{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T04:19:34Z","timestamp":1787545174670,"version":"build-2736575974"},"reference-count":221,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Chinese Institutes for Medical Research, Beijing","award":["CX25YZ13"],"award-info":[{"award-number":["CX25YZ13"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1303003"],"award-info":[{"award-number":["2022YFA1303003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National\u00a0Clinical\u00a0Key\u00a0Specialty\u00a0Construction\u00a0Program,\u00a0P.\u00a0R.China"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Neurodegener"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuroinflammation is no longer a secondary feature of amyotrophic lateral sclerosis (ALS), but rather a disease-modifying process that actively shapes the motor neuron vulnerability from the earliest stages of pathology. Central and peripheral immune cells, including microglia, astrocytes, and infiltrating T lymphocytes, adopt context-dependent states that can be neuroprotective or neurotoxic depending on disease stage and genetic background. These states are driven by discrete molecular programs, such as cGAS-STING-mediated innate immune sensing, NLRP3 inflammasome activation, and RIPK1-dependent necroptotic signaling, which represent tractable therapeutic targets. The repeated failure of broad-spectrum immunosuppressive trials reflects a fundamental mismatch between the non-selective interventions and the mechanistically distinct immune states of diseases. Converging transcriptomic, genetic, and immunophenotypic evidence supports the existence of putative neuroimmune endotypes in ALS, though this framework remains a working hypothesis pending prospective validation in biomarker-stratified cohorts. Advances in the following three domains are needed for realizing precision immunotherapy: standardized biomarker panels (including cerebrospinal fluid chitinases and TSPO-PET) to stratify patients by inflammatory subtype; pharmacodynamic readouts to confirm target engagement before interpreting clinical outcomes; and adaptive platform trial designs capable of evaluating mechanism-matching interventions in defined subgroups. This review integrates ALS-associated neuroinflammation with emerging precision medicine strategies, arguing that the central translational question is no longer whether or not to target neuroinflammation, but how, when, and in whom neuroinflammation should be targeted.<\/jats:p>","DOI":"10.1186\/s40035-026-00572-2","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T03:05:14Z","timestamp":1787540714000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis"],"prefix":"10.1186","volume":"15","author":[{"given":"Lu","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"issue":"5","key":"572_CR1","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/S1474-4422(21)00414-2","volume":"21","author":"SA Goutman","year":"2022","unstructured":"Goutman SA, Hardiman O, Al-Chalabi A, Chi\u00f3 A, Savelieff MG, Kiernan MC, et al. Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis. Lancet Neurol. 2022;21(5):465\u201379.","journal-title":"Lancet Neurol"},{"issue":"10","key":"572_CR2","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1001\/archneur.1997.00550220050013","volume":"54","author":"RH Brown","year":"1997","unstructured":"Brown RH. Amyotrophic lateral sclerosis. Insights Genet Arch Neurol. 1997;54(10):1246\u201350.","journal-title":"Insights Genet Arch Neurol"},{"issue":"1","key":"572_CR3","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","volume":"8","author":"W Zhang","year":"2023","unstructured":"Zhang W, Xiao D, Mao Q, Xia H. Role of neuroinflammation in neurodegeneration development. Signal Transduct Target Ther. 2023;8(1):267.","journal-title":"Signal Transduct Target Ther"},{"issue":"2","key":"572_CR4","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/S1474-4422(18)30394-6","volume":"18","author":"DR Beers","year":"2019","unstructured":"Beers DR, Appel SH. Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies. Lancet Neurol. 2019;18(2):211\u201320.","journal-title":"Lancet Neurol"},{"issue":"4","key":"572_CR5","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","volume":"186","author":"DM Wilson","year":"2023","unstructured":"Wilson DM, Cookson MR, Van Den Bosch L, Zetterberg H, Holtzman DM, Dewachter I. Hallmarks of neurodegenerative diseases. Cell. 2023;186(4):693\u2013714.","journal-title":"Cell"},{"issue":"1","key":"572_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00525-z","volume":"17","author":"P Masrori","year":"2022","unstructured":"Masrori P, Beckers J, Gossye H, Van Damme P. The role of inflammation in neurodegeneration: novel insights into the role of the immune system in C9orf72 HRE-mediated ALS\/FTD. Mol Neurodegener. 2022;17(1):22.","journal-title":"Mol Neurodegener"},{"issue":"9","key":"572_CR7","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1002\/acn3.51112","volume":"7","author":"G Tondo","year":"2020","unstructured":"Tondo G, Iaccarino L, Cerami C, Vanoli GE, Presotto L, Masiello V, et al. 11 C-PK11195 PET-based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2020;7(9):1513\u201323.","journal-title":"Ann Clin Transl Neurol"},{"issue":"Suppl","key":"572_CR8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/0022-510X(96)00073-1","volume":"139","author":"D Schiffer","year":"1996","unstructured":"Schiffer D, Cordera S, Cavalla P, Migheli A. Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis. J Neurol Sci. 1996;139(Suppl):27\u201333.","journal-title":"J Neurol Sci"},{"issue":"2","key":"572_CR9","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/ana.10805","volume":"55","author":"JS Henkel","year":"2004","unstructured":"Henkel JS, Engelhardt JI, Sikl\u00f3s L, Simpson EP, Kim SH, Pan T, et al. Presence of dendritic cells, MCP-1, and activated microglia\/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol. 2004;55(2):221\u201335.","journal-title":"Ann Neurol"},{"issue":"5","key":"572_CR10","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89530","volume":"2","author":"DR Beers","year":"2017","unstructured":"Beers DR, Zhao W, Wang J, Zhang X, Wen S, Neal D, et al. ALS patients\u2019 regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. JCI Insight. 2017;2(5):e89530.","journal-title":"JCI Insight"},{"issue":"5","key":"572_CR11","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1097\/WCO.0000000000001279","volume":"37","author":"AD Calma","year":"2024","unstructured":"Calma AD, Pavey N, Menon P, Vucic S. Neuroinflammation in amyotrophic lateral sclerosis: pathogenic insights and therapeutic implications. Curr Opin Neurol. 2024;37(5):585\u201392.","journal-title":"Curr Opin Neurol"},{"issue":"6753","key":"572_CR12","doi-asserted-by":"publisher","DOI":"10.1126\/science.adx0043","volume":"388","author":"FD Shi","year":"2025","unstructured":"Shi FD, Yong VW. Neuroinflammation across neurological diseases. Science. 2025;388(6753):eadx0043.","journal-title":"Science"},{"issue":"721","key":"572_CR13","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adj9332","volume":"15","author":"TF Gendron","year":"2023","unstructured":"Gendron TF, Petrucelli L. Immunological drivers of amyotrophic lateral sclerosis. Sci Transl Med. 2023;15(721):eadj9332.","journal-title":"Sci Transl Med"},{"issue":"5","key":"572_CR14","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.neuron.2014.01.011","volume":"81","author":"DB Re","year":"2014","unstructured":"Re DB, Le Verche V, Yu C, Amoroso MW, Politi KA, Phani S, et al. Necroptosis drives motor neuron death in models of both sporadic and familial ALS. Neuron. 2014;81(5):1001\u20138.","journal-title":"Neuron"},{"issue":"5","key":"572_CR15","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.neuron.2014.01.013","volume":"81","author":"AE Frakes","year":"2014","unstructured":"Frakes AE, Ferraiuolo L, Haidet-Phillips AM, Schmelzer L, Braun L, Miranda CJ, et al. Microglia induce motor neuron death via the classical NF-\u03baB pathway in amyotrophic lateral sclerosis. Neuron. 2014;81(5):1009\u201323.","journal-title":"Neuron"},{"issue":"2","key":"572_CR16","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41582-024-01049-4","volume":"21","author":"K Faller","year":"2025","unstructured":"Faller K, Chaytow H, Gillingwater TH. Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis. Nat Rev Neurol. 2025;21(2):86\u2013102.","journal-title":"Nat Rev Neurol"},{"issue":"8","key":"572_CR17","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/s41582-019-0227-8","volume":"15","author":"NE Gilhus","year":"2019","unstructured":"Gilhus NE, Deuschl G. Neuroinflammation\u2014a common thread in neurological disorders. Nat Rev Neurol. 2019;15(8):429\u201330.","journal-title":"Nat Rev Neurol"},{"issue":"5726","key":"572_CR18","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1126\/science.1110647","volume":"308","author":"A Nimmerjahn","year":"2005","unstructured":"Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308(5726):1314\u20138.","journal-title":"Science"},{"issue":"12","key":"572_CR19","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.1093\/brain\/awaa309","volume":"143","author":"BE Clarke","year":"2020","unstructured":"Clarke BE, Patani R. The microglial component of amyotrophic lateral sclerosis. Brain. 2020;143(12):3526\u201339.","journal-title":"Brain"},{"issue":"3","key":"572_CR20","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1002\/glia.22444","volume":"61","author":"K Roberts","year":"2013","unstructured":"Roberts K, Zeineddine R, Corcoran L, Li W, Campbell IL, Yerbury JJ. Extracellular aggregated Cu\/Zn superoxide dismutase activates microglia to give a cytotoxic phenotype. Glia. 2013;61(3):409\u201319.","journal-title":"Glia"},{"issue":"3","key":"572_CR21","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00401-011-0932-x","volume":"123","author":"J Brettschneider","year":"2012","unstructured":"Brettschneider J, Libon DJ, Toledo JB, Xie SX, McCluskey L, Elman L, et al. Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis. Acta Neuropathol. 2012;123(3):395\u2013407.","journal-title":"Acta Neuropathol"},{"issue":"12","key":"572_CR22","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.1093\/hmg\/ddv094","volume":"24","author":"M Bowerman","year":"2015","unstructured":"Bowerman M, Salsac C, Coque E, Eiselt \u00c9, Deschaumes RG, Brodovitch A, et al. Tweak regulates astrogliosis, microgliosis and skeletal muscle atrophy in a mouse model of amyotrophic lateral sclerosis. Hum Mol Genet. 2015;24(12):3440\u201356.","journal-title":"Hum Mol Genet"},{"issue":"2","key":"572_CR23","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/glia.23728","volume":"68","author":"V Deora","year":"2020","unstructured":"Deora V, Lee JD, Albornoz EA, McAlary L, Jagaraj CJ, Robertson A, et al. The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins. Glia. 2020;68(2):407\u201321.","journal-title":"Glia"},{"issue":"6","key":"572_CR24","doi-asserted-by":"publisher","first-page":"421","DOI":"10.3390\/cells14060421","volume":"14","author":"S Bond","year":"2025","unstructured":"Bond S, Saxena S, Sierra-Delgado JA. Microglia in ALS: insights into mechanisms and therapeutic potential. Cells. 2025;14(6):421.","journal-title":"Cells"},{"key":"572_CR25","first-page":"0548","volume":"7","author":"LX Chen","year":"2024","unstructured":"Chen LX, Zhang MD, Xu HF, Ye HQ, Chen DF, Wang PS, et al. Single-nucleus RNA sequencing reveals the spatiotemporal dynamics of disease-associated microglia in amyotrophic lateral sclerosis. Research (Wash D C). 2024;7:0548.","journal-title":"Research (Wash D C)"},{"issue":"6435","key":"572_CR26","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.aav9776","volume":"364","author":"S Maniatis","year":"2019","unstructured":"Maniatis S, \u00c4ij\u00f6 T, Vickovic S, Braine C, Kang K, Mollbrink A, et al. Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis. Science. 2019;364(6435):89\u201393.","journal-title":"Science"},{"issue":"4","key":"572_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036000","volume":"7","author":"YN Gerber","year":"2012","unstructured":"Gerber YN, Sabourin JC, Rabano M, Md V, Perrin FE. Early functional deficit and microglial disturbances in a mouse model of amyotrophic lateral sclerosis. PLoS ONE. 2012;7(4):e36000.","journal-title":"PLoS ONE"},{"issue":"21","key":"572_CR28","doi-asserted-by":"publisher","first-page":"7594","DOI":"10.1073\/pnas.0802556105","volume":"105","author":"K Yamanaka","year":"2008","unstructured":"Yamanaka K, Boillee S, Roberts EA, Garcia ML, McAlonis-Downes M, Mikse OR, et al. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc Natl Acad Sci U S A. 2008;105(21):7594\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5778","key":"572_CR29","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1126\/science.1123511","volume":"312","author":"S Boill\u00e9e","year":"2006","unstructured":"Boill\u00e9e S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006;312(5778):1389\u201392.","journal-title":"Science"},{"issue":"5642","key":"572_CR30","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1126\/science.1086071","volume":"302","author":"AM Clement","year":"2003","unstructured":"Clement AM, Nguyen MD, Roberts EA, Garcia ML, Boill\u00e9e S, Rule M, et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science. 2003;302(5642):113\u20137.","journal-title":"Science"},{"issue":"1","key":"572_CR31","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.expneurol.2012.06.011","volume":"237","author":"B Liao","year":"2012","unstructured":"Liao B, Zhao W, Beers DR, Henkel JS, Appel SH. Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Exp Neurol. 2012;237(1):147\u201352.","journal-title":"Exp Neurol"},{"key":"572_CR32","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/1471-2202-12-91","volume":"12","author":"SA Sargsyan","year":"2011","unstructured":"Sargsyan SA, Blackburn DJ, Barber SC, Grosskreutz J, De Vos KJ, Monk PN, et al. A comparison of in vitro properties of resting SOD1 transgenic microglia reveals evidence of reduced neuroprotective function. BMC Neurosci. 2011;12:91.","journal-title":"BMC Neurosci"},{"issue":"1","key":"572_CR33","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12974-022-02421-1","volume":"19","author":"H Quek","year":"2022","unstructured":"Quek H, Cun\u00ed-L\u00f3pez C, Stewart R, Colletti T, Notaro A, Nguyen TH, et al. ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated with disease progression. J Neuroinflammation. 2022;19(1):58.","journal-title":"J Neuroinflammation"},{"issue":"4","key":"572_CR34","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.stem.2010.08.014","volume":"7","author":"A Sierra","year":"2010","unstructured":"Sierra A, Encinas JM, Deudero JJ, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, et al. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell. 2010;7(4):483\u201395.","journal-title":"Cell Stem Cell"},{"issue":"2","key":"572_CR35","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1007\/s12035-014-9070-5","volume":"53","author":"Y Tang","year":"2016","unstructured":"Tang Y, Le W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol. 2016;53(2):1181\u201394.","journal-title":"Mol Neurobiol"},{"issue":"1","key":"572_CR36","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/nn.3599","volume":"17","author":"O Butovsky","year":"2014","unstructured":"Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, et al. Identification of a unique TGF-\u03b2-dependent molecular and functional signature in microglia. Nat Neurosci. 2014;17(1):131\u201343.","journal-title":"Nat Neurosci"},{"issue":"11","key":"572_CR37","doi-asserted-by":"publisher","first-page":"2994","DOI":"10.3390\/biomedicines11112994","volume":"11","author":"C Jauregui","year":"2023","unstructured":"Jauregui C, Blanco-Luquin I, Mac\u00edas M, Roldan M, Caballero C, Pagola I, et al. Exploring the disease-associated microglia state in amyotrophic lateral sclerosis. Biomedicines.\u00a02023;11(11):2994.","journal-title":"Biomedicines"},{"issue":"10","key":"572_CR38","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41583-018-0057-5","volume":"19","author":"O Butovsky","year":"2018","unstructured":"Butovsky O, Weiner HL. Microglial signatures and their role in health and disease. Nat Rev Neurosci. 2018;19(10):622\u201335.","journal-title":"Nat Rev Neurosci"},{"issue":"3","key":"572_CR39","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","volume":"47","author":"S Krasemann","year":"2017","unstructured":"Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity. 2017;47(3):566-81.e9.","journal-title":"Immunity"},{"issue":"1","key":"572_CR40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40478-016-0306-7","volume":"4","author":"P Rizzu","year":"2016","unstructured":"Rizzu P, Blauwendraat C, Heetveld S, Lynes EM, Castillo-Lizardo M, Dhingra A, et al. C9orf72 is differentially expressed in the central nervous system and myeloid cells and consistently reduced in C9orf72, MAPT and GRN mutation carriers. Acta Neuropathol Commun. 2016;4(1):37.","journal-title":"Acta Neuropathol Commun"},{"issue":"11","key":"572_CR41","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1038\/s41593-025-02075-1","volume":"28","author":"P Masrori","year":"2025","unstructured":"Masrori P, Bijnens B, Fumagalli L, Davie K, Poovathingal SK, Meese T, et al. C9orf72 hexanucleotide repeat expansions impair microglial response in ALS. Nat Neurosci. 2025;28(11):2217\u201330.","journal-title":"Nat Neurosci"},{"issue":"6279","key":"572_CR42","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1126\/science.aaf1064","volume":"351","author":"JG O\u2019Rourke","year":"2016","unstructured":"O\u2019Rourke JG, Bogdanik L, Y\u00e1\u00f1ez A, Lall D, Wolf AJ, Muhammad AK, et al. C9orf72 is required for proper macrophage and microglial function in mice. Science. 2016;351(6279):1324\u20139.","journal-title":"Science"},{"key":"572_CR43","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.neures.2017.09.011","volume":"126","author":"K Yamanaka","year":"2018","unstructured":"Yamanaka K, Komine O. The multi-dimensional roles of astrocytes in ALS. Neurosci Res. 2018;126:31\u20138.","journal-title":"Neurosci Res"},{"issue":"5","key":"572_CR44","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nn1876","volume":"10","author":"M Nagai","year":"2007","unstructured":"Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci. 2007;10(5):615\u201322.","journal-title":"Nat Neurosci"},{"issue":"5","key":"572_CR45","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/nn1885","volume":"10","author":"FP Di Giorgio","year":"2007","unstructured":"Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci. 2007;10(5):608\u201314.","journal-title":"Nat Neurosci"},{"issue":"43","key":"572_CR46","doi-asserted-by":"publisher","first-page":"17803","DOI":"10.1073\/pnas.1103141108","volume":"108","author":"ST Papadeas","year":"2011","unstructured":"Papadeas ST, Kraig SE, O\u2019Banion C, Lepore AC, Maragakis NJ. Astrocytes carrying the superoxide dismutase 1 (SOD1G93A) mutation induce wild-type motor neuron degeneration in vivo. Proc Natl Acad Sci U S A. 2011;108(43):17803\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"572_CR47","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1073\/pnas.1314085111","volume":"111","author":"K Meyer","year":"2014","unstructured":"Meyer K, Ferraiuolo L, Miranda CJ, Likhite S, McElroy S, Renusch S, et al. Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS. Proc Natl Acad Sci U S A. 2014;111(2):829\u201332.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"572_CR48","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41583-022-00641-1","volume":"24","author":"AN Brandebura","year":"2023","unstructured":"Brandebura AN, Paumier A, Onur TS, Allen NJ. Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders. Nat Rev Neurosci. 2023;24(1):23\u201339.","journal-title":"Nat Rev Neurosci"},{"issue":"33","key":"572_CR49","first-page":"5037","volume":"23","author":"M Peric","year":"2017","unstructured":"Peric M, Mitrecic D, Andjus PR. Targeting astrocytes for treatment in amyotrophic lateral sclerosis. Curr Pharm Des. 2017;23(33):5037\u201344.","journal-title":"Curr Pharm Des"},{"key":"572_CR50","doi-asserted-by":"publisher","first-page":"107559","DOI":"10.1016\/j.neuropharm.2019.03.002","volume":"161","author":"E Pajarillo","year":"2019","unstructured":"Pajarillo E, Rizor A, Lee J, Aschner M, Lee E. The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: potential targets for neurotherapeutics. Neuropharmacology. 2019;161:107559.","journal-title":"Neuropharmacology"},{"issue":"1","key":"572_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00665-w","volume":"18","author":"M Xie","year":"2023","unstructured":"Xie M, Pallegar PN, Parusel S, Nguyen AT, Wu LJ. Regulation of cortical hyperexcitability in amyotrophic lateral sclerosis: focusing on glial mechanisms. Mol Neurodegener. 2023;18(1):75.","journal-title":"Mol Neurodegener"},{"issue":"5","key":"572_CR52","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.cell.2011.02.018","volume":"144","author":"A Suzuki","year":"2011","unstructured":"Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, et al. Astrocyte-neuron lactate transport is required for long-term memory formation. Cell. 2011;144(5):810\u201323.","journal-title":"Cell"},{"issue":"8023","key":"572_CR53","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/s41586-024-07611-w","volume":"632","author":"SM Theparambil","year":"2024","unstructured":"Theparambil SM, Kopach O, Braga A, Nizari S, Hosford PS, Sagi-Kiss V, et al. Adenosine signalling to astrocytes coordinates brain metabolism and function. Nature. 2024;632(8023):139\u201346.","journal-title":"Nature"},{"issue":"1","key":"572_CR54","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-022-00785-3","volume":"29","author":"A Gyawali","year":"2022","unstructured":"Gyawali A, Latif S, Choi SH, Hyeon SJ, Ryu H, Kang YS. Monocarboxylate transporter functions and neuroprotective effects of valproic acid in experimental models of amyotrophic lateral sclerosis. J Biomed Sci. 2022;29(1):2.","journal-title":"J Biomed Sci"},{"issue":"2","key":"572_CR55","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.neuron.2018.03.010","volume":"98","author":"KW Kelley","year":"2018","unstructured":"Kelley KW, Ben Haim L, Schirmer L, Tyzack GE, Tolman M, Miller JG, et al. Kir4.1-dependent astrocyte-fast motor neuron interactions are required for peak strength. Neuron. 2018;98(2):306-19.e7.","journal-title":"Neuron"},{"issue":"10","key":"572_CR56","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1002\/glia.24435","volume":"71","author":"R Stevenson","year":"2023","unstructured":"Stevenson R, Samokhina E, Mangat A, Rossetti I, Purushotham SS, Malladi CS, et al. Astrocytic K+ clearance during disease progression in amyotrophic lateral sclerosis. Glia. 2023;71(10):2456\u201372.","journal-title":"Glia"},{"issue":"2","key":"572_CR57","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.3892\/mmr.2017.6786","volume":"16","author":"J Dai","year":"2017","unstructured":"Dai J, Lin W, Zheng M, Liu Q, He B, Luo C, et al. Alterations in AQP4 expression and polarization in the course of motor neuron degeneration in SOD1G93A mice. Mol Med Rep. 2017;16(2):1739\u201346.","journal-title":"Mol Med Rep"},{"issue":"1","key":"572_CR58","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1038\/s41467-020-17514-9","volume":"11","author":"KA Guttenplan","year":"2020","unstructured":"Guttenplan KA, Weigel MK, Adler DI, Couthouis J, Liddelow SA, Gitler AD, et al. Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model. Nat Commun. 2020;11(1):3753.","journal-title":"Nat Commun"},{"key":"572_CR59","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.brainresbull.2022.08.015","volume":"189","author":"TE Murray","year":"2022","unstructured":"Murray TE, Richards CM, Robert-Gostlin VN, Bernath AK, Lindhout IA, Klegeris A. Potential neurotoxic activity of diverse molecules released by astrocytes. Brain Res Bull. 2022;189:80\u2013101.","journal-title":"Brain Res Bull"},{"issue":"9","key":"572_CR60","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.1172\/JCI90610","volume":"127","author":"T Philips","year":"2017","unstructured":"Philips T, Rothstein JD. Oligodendroglia: metabolic supporters of neurons. J Clin Invest. 2017;127(9):3271\u201380.","journal-title":"J Clin Invest"},{"key":"572_CR61","doi-asserted-by":"crossref","unstructured":"Mouhi S, Pio T, Andersen J. Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models. Trends Cell Biol.\u00a02025:S0962-8924(25)00251-X.","DOI":"10.1016\/j.tcb.2025.11.003"},{"issue":"10","key":"572_CR62","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.4103\/1673-5374.368302","volume":"18","author":"KH Schuster","year":"2023","unstructured":"Schuster KH, McLoughlin HS. Disease-associated oligodendrocyte signatures in neurodegenerative disease: the known and unknown. Neural Regen Res. 2023;18(10):2192\u20133.","journal-title":"Neural Regen Res"},{"issue":"7","key":"572_CR63","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1038\/s41593-022-01104-7","volume":"25","author":"M Kenigsbuch","year":"2022","unstructured":"Kenigsbuch M, Bost P, Halevi S, Chang Y, Chen S, Ma Q, et al. A shared disease-associated oligodendrocyte signature among multiple CNS pathologies. Nat Neurosci. 2022;25(7):876\u201386.","journal-title":"Nat Neurosci"},{"issue":"8","key":"572_CR64","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111189","volume":"40","author":"S Pandey","year":"2022","unstructured":"Pandey S, Shen K, Lee SH, Shen YA, Wang Y, Otero-Garc\u00eda M, et al. Disease-associated oligodendrocyte responses across neurodegenerative diseases. Cell Rep. 2022;40(8):111189.","journal-title":"Cell Rep"},{"issue":"1","key":"572_CR65","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s40478-024-01893-x","volume":"12","author":"M Horiuchi","year":"2024","unstructured":"Horiuchi M, Watanabe S, Komine O, Takahashi E, Kaneko K, Itohara S, et al. ALS-linked mutant TDP-43 in oligodendrocytes induces oligodendrocyte damage and exacerbates motor dysfunction in mice. Acta Neuropathol Commun. 2024;12(1):184.","journal-title":"Acta Neuropathol Commun"},{"issue":"1","key":"572_CR66","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1002\/alz.12612","volume":"19","author":"K Connolly","year":"2023","unstructured":"Connolly K, Lehoux M, O\u2019Rourke R, Assetta B, Erdemir GA, Elias JA, et al. Potential role of chitinase-3-like protein 1 (CHI3L1\/YKL-40) in neurodegeneration and Alzheimer\u2019s disease. Alzheimers Dement. 2023;19(1):9\u201324.","journal-title":"Alzheimers Dement"},{"issue":"8","key":"572_CR67","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1038\/cdd.2014.35","volume":"21","author":"M Bonora","year":"2014","unstructured":"Bonora M, De Marchi E, Patergnani S, Suski JM, Celsi F, Bononi A, et al. Tumor necrosis factor-\u03b1 impairs oligodendroglial differentiation through a mitochondria-dependent process. Cell Death Differ. 2014;21(8):1198\u2013208.","journal-title":"Cell Death Differ"},{"issue":"1","key":"572_CR68","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/s41593-022-01205-3","volume":"26","author":"J Humphrey","year":"2023","unstructured":"Humphrey J, Venkatesh S, Hasan R, Herb JT, de Paiva Lopes K, K\u00fc\u00e7\u00fckali F, et al. Integrative transcriptomic analysis of the amyotrophic lateral sclerosis spinal cord implicates glial activation and suggests new risk genes. Nat Neurosci. 2023;26(1):150\u201362.","journal-title":"Nat Neurosci"},{"issue":"12","key":"572_CR69","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1001\/jamaneurol.2017.2255","volume":"74","author":"BJ Murdock","year":"2017","unstructured":"Murdock BJ, Zhou T, Kashlan SR, Little RJ, Goutman SA, Feldman EL. Correlation of peripheral immunity with rapid amyotrophic lateral sclerosis progression. JAMA Neurol. 2017;74(12):1446\u201354.","journal-title":"JAMA Neurol"},{"issue":"7","key":"572_CR70","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.4103\/NRR.NRR-D-24-01081","volume":"21","author":"Z Wang","year":"2025","unstructured":"Wang Z, Cao W, Chen L, Zhang S, Tang L, Cui W, et al. The role of the peripheral immune system in mediating axonal dysfunction in early-stage amyotrophic lateral sclerosis: an age- and sex-based analysis. Neural Regen Res.\u00a02026;21(7):3156\u201362.","journal-title":"Neural Regen Res"},{"key":"572_CR71","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.890958","volume":"14","author":"W Yu","year":"2022","unstructured":"Yu W, He J, Cai X, Yu Z, Zou Z, Fan D. Neuroimmune crosstalk between the peripheral and the central immune system in amyotrophic lateral sclerosis. Front Aging Neurosci. 2022;14:890958.","journal-title":"Front Aging Neurosci"},{"issue":"8","key":"572_CR72","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.3390\/pharmaceutics17081041","volume":"17","author":"HM Yang","year":"2025","unstructured":"Yang HM. Overcoming the blood-brain barrier: advanced strategies in targeted drug delivery for neurodegenerative diseases. Pharmaceutics.\u00a02025;17(8):1041.","journal-title":"Pharmaceutics"},{"issue":"16","key":"572_CR73","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ads0505","volume":"11","author":"A Cheemala","year":"2025","unstructured":"Cheemala A, Kimble AL, Burrage EN, Helming SB, Tyburski JD, Leclair NK, et al. Amyotrophic lateral sclerosis and frontotemporal dementia mutation reduces endothelial TDP-43 and causes blood-brain barrier defects. Sci Adv. 2025;11(16):eads0505.","journal-title":"Sci Adv"},{"issue":"1","key":"572_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-62756-8","volume":"10","author":"M Jin","year":"2020","unstructured":"Jin M, G\u00fcnther R, Akg\u00fcn K, Hermann A, Ziemssen T. Peripheral proinflammatory Th1\/Th17 immune cell shift is linked to disease severity in amyotrophic lateral sclerosis. Sci Rep. 2020;10(1):5941.","journal-title":"Sci Rep"},{"issue":"1","key":"572_CR75","doi-asserted-by":"publisher","first-page":"6733","DOI":"10.1038\/s41467-022-34526-9","volume":"13","author":"S Yazdani","year":"2022","unstructured":"Yazdani S, Seitz C, Cui C, Lovik A, Pan L, Piehl F, et al. T cell responses at diagnosis of amyotrophic lateral sclerosis predict disease progression. Nat Commun. 2022;13(1):6733.","journal-title":"Nat Commun"},{"issue":"6","key":"572_CR76","doi-asserted-by":"publisher","first-page":"3370","DOI":"10.3390\/ijms23063370","volume":"23","author":"O Yildiz","year":"2022","unstructured":"Yildiz O, Schroth J, Lombardi V, Pucino V, Bobeva Y, Yip PK, et al. The expression of active CD11b monocytes in blood and disease progression in amyotrophic lateral sclerosis. Int J Mol Sci.\u00a02022;23(6):3370.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"572_CR77","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12974-025-03347-0","volume":"22","author":"E \u00c1lvarez-S\u00e1nchez","year":"2025","unstructured":"\u00c1lvarez-S\u00e1nchez E, Carbayo \u00c1, Valle-Tamayo N, Mu\u00f1oz L, Aumatell J, Torres S, et al. Single-cell RNA sequencing highlights the role of distinct natural killer subsets in sporadic amyotrophic lateral sclerosis. J Neuroinflammation. 2025;22(1):15.","journal-title":"J Neuroinflammation"},{"issue":"3","key":"572_CR78","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.cell.2020.09.020","volume":"183","author":"CH Yu","year":"2020","unstructured":"Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, et al. TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS\/STING in ALS. Cell. 2020;183(3):636-49.e18.","journal-title":"Cell"},{"issue":"1-2","key":"572_CR79","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jneuroim.2010.03.004","volume":"222","author":"T Tateishi","year":"2010","unstructured":"Tateishi T, Yamasaki R, Tanaka M, Matsushita T, Kikuchi H, Isobe N, et al. CSF chemokine alterations related to the clinical course of amyotrophic lateral sclerosis. J Neuroimmunol. 2010;222(1\u20132):76\u201381.","journal-title":"J Neuroimmunol"},{"issue":"12","key":"572_CR80","first-page":"1338","volume":"90","author":"B Gille","year":"2019","unstructured":"Gille B, De Schaepdryver M, Dedeene L, Goossens J, Claeys KG, Van Den Bosch L, et al. Inflammatory markers in cerebrospinal fluid: independent prognostic biomarkers in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(12):1338\u201346.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"46","key":"572_CR81","doi-asserted-by":"publisher","first-page":"17913","DOI":"10.1073\/pnas.0804610105","volume":"105","author":"IM Chiu","year":"2008","unstructured":"Chiu IM, Chen A, Zheng Y, Kosaras B, Tsiftsoglou SA, Vartanian TK, et al. T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc Natl Acad Sci U S A. 2008;105(46):17913\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"572_CR82","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41577-023-00960-z","volume":"24","author":"A Liston","year":"2024","unstructured":"Liston A, Pasciuto E, Fitzgerald DC, Yshii L. Brain regulatory T cells. Nat Rev Immunol. 2024;24(5):326\u201337.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"572_CR83","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03327-w","volume":"21","author":"T Itou","year":"2024","unstructured":"Itou T, Fujita K, Okuzono Y, Warude D, Miyakawa S, Mihara Y, et al. Th17 and effector CD8 T cells relate to disease progression in amyotrophic lateral sclerosis: a case control study. J Neuroinflammation. 2024;21(1):331.","journal-title":"J Neuroinflammation"},{"issue":"6","key":"572_CR84","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae428","volume":"6","author":"HJ Kim","year":"2024","unstructured":"Kim HJ, Ban JJ, Kang J, Im HR, Ko SH, Sung JJ, et al. Single-cell analysis reveals expanded CD8+ GZMK high T cells in CSF and shared peripheral clones in sporadic amyotrophic lateral sclerosis. Brain Commun. 2024;6(6):fcae428.","journal-title":"Brain Commun"},{"issue":"11","key":"572_CR85","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1172\/JCI17702","volume":"112","author":"A Trenado","year":"2003","unstructured":"Trenado A, Charlotte F, Fisson S, Yagello M, Klatzmann D, Salomon BL, et al. Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia. J Clin Invest. 2003;112(11):1688\u201396.","journal-title":"J Clin Invest"},{"issue":"7","key":"572_CR86","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1172\/JCI23963","volume":"115","author":"D Valmori","year":"2005","unstructured":"Valmori D, Merlo A, Souleimanian NE, Hesdorffer CS, Ayyoub M. A peripheral circulating compartment of natural naive CD4 Tregs. J Clin Invest. 2005;115(7):1953\u201362.","journal-title":"J Clin Invest"},{"issue":"1","key":"572_CR87","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/emmm.201201544","volume":"5","author":"JS Henkel","year":"2013","unstructured":"Henkel JS, Beers DR, Wen S, Rivera AL, Toennis KM, Appel JE, et al. Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol Med. 2013;5(1):64\u201379.","journal-title":"EMBO Mol Med"},{"issue":"6","key":"572_CR88","doi-asserted-by":"publisher","first-page":"2312","DOI":"10.1073\/pnas.1815961116","volume":"116","author":"E Coque","year":"2019","unstructured":"Coque E, Salsac C, Espinosa-Carrasco G, Varga B, Degauque N, Cadoux M, et al. Cytotoxic CD8+ T lymphocytes expressing ALS-causing SOD1 mutant selectively trigger death of spinal motoneurons. Proc Natl Acad Sci USA. 2019;116(6):2312\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"21","key":"572_CR89","doi-asserted-by":"publisher","first-page":"3431","DOI":"10.3390\/cells11213431","volume":"11","author":"K Kaur","year":"2022","unstructured":"Kaur K, Chen PC, Ko MW, Mei A, Chovatiya N, Huerta-Yepez S, et al. The potential role of cytotoxic immune effectors in induction, progression and pathogenesis of amyotrophic lateral sclerosis (ALS). Cells.\u00a02022;11(21):3431.","journal-title":"Cells"},{"issue":"1","key":"572_CR90","doi-asserted-by":"publisher","first-page":"e200042","DOI":"10.1212\/NXI.0000000000200042","volume":"10","author":"O Yildiz","year":"2023","unstructured":"Yildiz O, Schroth J, Tree T, Turner MR, Shaw PJ, Henson SM, et al. Senescent-like blood lymphocytes and disease progression in amyotrophic lateral sclerosis. Neurol Neuroimmunol Neuroinflamm.\u00a02022;10(1):e200042.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"1","key":"572_CR91","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12950-025-00460-y","volume":"22","author":"V Tsang","year":"2025","unstructured":"Tsang V, Malaspina A, Henson SM. The metabolic intersection between immunosenescence and neuroinflammation in amyotrophic lateral sclerosis. J Inflamm (Lond). 2025;22(1):36.","journal-title":"J Inflamm (Lond)"},{"issue":"11","key":"572_CR92","doi-asserted-by":"publisher","first-page":"928","DOI":"10.3390\/cells13110928","volume":"13","author":"AR Dashtmian","year":"2024","unstructured":"Dashtmian AR, Darvishi FB, Arnold WD. Chronological and biological aging in amyotrophic lateral sclerosis and the potential of senolytic therapies. Cells.\u00a02024;13(11):928.","journal-title":"Cells"},{"issue":"13","key":"572_CR93","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202302659R","volume":"38","author":"RF S\u00eerbulescu","year":"2024","unstructured":"S\u00eerbulescu RF, Nicholson K, Kawai K, Hilton OM, Sobell D, Jin G, et al. Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis. FASEB J. 2024;38(13):e23796.","journal-title":"FASEB J"},{"issue":"3","key":"572_CR94","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1172\/JCI85113","volume":"127","author":"C Mauri","year":"2017","unstructured":"Mauri C, Menon M. Human regulatory B cells in health and disease: therapeutic potential. J Clin Invest. 2017;127(3):772\u20139.","journal-title":"J Clin Invest"},{"issue":"1","key":"572_CR95","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02812-y","volume":"20","author":"LJ Dwyer","year":"2023","unstructured":"Dwyer LJ, Maheshwari S, Levy E, Poznansky MC, Whalen MJ, S\u00eerbulescu RF. B cell treatment promotes a neuroprotective microenvironment after traumatic brain injury through reciprocal immunomodulation with infiltrating peripheral myeloid cells. J Neuroinflammation. 2023;20(1):133.","journal-title":"J Neuroinflammation"},{"issue":"6","key":"572_CR96","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1001\/jamaneurol.2017.0357","volume":"74","author":"W Zhao","year":"2017","unstructured":"Zhao W, Beers DR, Hooten KG, Sieglaff DH, Zhang A, Kalyana-Sundaram S, et al. Characterization of gene expression phenotype in amyotrophic lateral sclerosis monocytes. JAMA Neurol. 2017;74(6):677\u201385.","journal-title":"JAMA Neurol"},{"key":"572_CR97","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00279","volume":"11","author":"PA McCombe","year":"2020","unstructured":"McCombe PA, Lee JD, Woodruff TM, Henderson RD. The peripheral immune system and amyotrophic lateral sclerosis. Front Neurol. 2020;11:279.","journal-title":"Front Neurol"},{"issue":"21","key":"572_CR98","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.3390\/cells11213364","volume":"11","author":"J Mills","year":"2022","unstructured":"Mills J, Ladner L, Soliman E, Leonard J, Morton PD, Theus MH. Cross-talk and subset control of microglia and associated myeloid cells in neurological disorders. Cells. 2022;11(21):3364.","journal-title":"Cells"},{"issue":"1","key":"572_CR99","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/brain\/awad304","volume":"147","author":"W Wen","year":"2024","unstructured":"Wen W, Cheng J, Tang Y. Brain perivascular macrophages: current understanding and future prospects. Brain. 2024;147(1):39\u201355.","journal-title":"Brain"},{"issue":"1","key":"572_CR100","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1038\/s41467-020-15644-8","volume":"11","author":"S Garofalo","year":"2020","unstructured":"Garofalo S, Cocozza G, Porzia A, Inghilleri M, Raspa M, Scavizzi F, et al. Natural killer cells modulate motor neuron-immune cell cross talk in models of amyotrophic lateral sclerosis. Nat Commun. 2020;11(1):1773.","journal-title":"Nat Commun"},{"issue":"11","key":"572_CR101","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1038\/s41593-020-00718-z","volume":"23","author":"A Chiot","year":"2020","unstructured":"Chiot A, Za\u00efdi S, Iltis C, Ribon M, Berriat F, Schiaffino L, et al. Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival. Nat Neurosci. 2020;23(11):1339\u201351.","journal-title":"Nat Neurosci"},{"key":"572_CR102","doi-asserted-by":"publisher","first-page":"1246768","DOI":"10.3389\/fimmu.2023.1246768","volume":"14","author":"W Cao","year":"2023","unstructured":"Cao W, Fan D. Neutrophils: a subgroup of neglected immune cells in ALS. Front Immunol. 2023;14:1246768.","journal-title":"Front Immunol"},{"issue":"8","key":"572_CR103","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.it.2007.06.002","volume":"28","author":"N Borregaard","year":"2007","unstructured":"Borregaard N, S\u00f8rensen OE, Theilgaard-M\u00f6nch K. Neutrophil granules: a library of innate immunity proteins. Trends Immunol. 2007;28(8):340\u20135.","journal-title":"Trends Immunol"},{"issue":"1","key":"572_CR104","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-57366-y","volume":"10","author":"SJ Choi","year":"2020","unstructured":"Choi SJ, Hong YH, Kim SM, Shin JY, Suh YJ, Sung JJ. High neutrophil-to-lymphocyte ratio predicts short survival duration in amyotrophic lateral sclerosis. Sci Rep. 2020;10(1):428.","journal-title":"Sci Rep"},{"issue":"6","key":"572_CR105","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/j.1600-0404.2008.01112.x","volume":"119","author":"D Keizman","year":"2009","unstructured":"Keizman D, Rogowski O, Berliner S, Ish-Shalom M, Maimon N, Nefussy B, et al. Low-grade systemic inflammation in patients with amyotrophic lateral sclerosis. Acta Neurol Scand. 2009;119(6):383\u20139.","journal-title":"Acta Neurol Scand"},{"issue":"4","key":"572_CR106","doi-asserted-by":"publisher","first-page":"875","DOI":"10.4103\/1673-5374.322476","volume":"17","author":"QQ Wei","year":"2022","unstructured":"Wei QQ, Hou YB, Zhang LY, Ou RW, Cao B, Chen YP, et al. Neutrophil-to-lymphocyte ratio in sporadic amyotrophic lateral sclerosis. Neural Regen Res. 2022;17(4):875\u201380.","journal-title":"Neural Regen Res"},{"key":"572_CR107","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8217663","volume":"2022","author":"J Peng","year":"2022","unstructured":"Peng J, Pan J, Mo J, Peng Y. MPO\/HOCl facilitates apoptosis and ferroptosis in the SOD1G93A motor neuron of amyotrophic lateral sclerosis. Oxid Med Cell Longev. 2022;2022:8217663.","journal-title":"Oxid Med Cell Longev"},{"issue":"3","key":"572_CR108","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/ana.78161","volume":"99","author":"W Cao","year":"2026","unstructured":"Cao W, Yu L, Wang Z, Deng B, Fan D. Neutrophil-secreted enzymes and ALS risk: exploring a potential mechanistic link. Ann Neurol. 2026;99(3):591\u2013605.","journal-title":"Ann Neurol"},{"issue":"2","key":"572_CR109","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032366","volume":"7","author":"M Saffarzadeh","year":"2012","unstructured":"Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, et al. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS ONE. 2012;7(2):e32366.","journal-title":"PLoS ONE"},{"issue":"5","key":"572_CR110","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1194\/jlr.M700535-JLR200","volume":"49","author":"U Singh","year":"2008","unstructured":"Singh U, Dasu MR, Yancey PG, Afify A, Devaraj S, Jialal I. Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in wistar rats. J Lipid Res. 2008;49(5):1015\u201323.","journal-title":"J Lipid Res"},{"issue":"9","key":"572_CR111","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073777","volume":"8","author":"X He","year":"2013","unstructured":"He X, Zhang L, Yao X, Hu J, Yu L, Jia H, et al. Association studies of MMP-9 in Parkinson\u2019s disease and amyotrophic lateral sclerosis. PLoS ONE. 2013;8(9):e73777.","journal-title":"PLoS ONE"},{"issue":"11","key":"572_CR112","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147129","volume":"6","author":"BJ Murdock","year":"2021","unstructured":"Murdock BJ, Famie JP, Piecuch CE, Pawlowski KD, Mendelson FE, Pieroni CH, et al. NK cells associate with ALS in a sex- and age-dependent manner. JCI Insight. 2021;6(11):e147129.","journal-title":"JCI Insight"},{"issue":"5","key":"572_CR113","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.immuni.2017.10.008","volume":"47","author":"AG Freud","year":"2017","unstructured":"Freud AG, Mundy-Bosse BL, Yu J, Caligiuri MA. The broad spectrum of human natural killer cell diversity. Immunity. 2017;47(5):820\u201333.","journal-title":"Immunity"},{"issue":"1","key":"572_CR114","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12974-024-03040-8","volume":"21","author":"C Rodriguez-Mogeda","year":"2024","unstructured":"Rodriguez-Mogeda C, van Ansenwoude C, van der Molen L, Strijbis E, Mebius RE, de Vries HE. The role of CD56bright NK cells in neurodegenerative disorders. J Neuroinflammation. 2024;21(1):48.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"572_CR115","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s00401-025-02913-3","volume":"150","author":"JF Tuddenham","year":"2025","unstructured":"Tuddenham JF, Fujita M, Lee E, Nimmagadda N, Khairallah A, Harbison C, et al. Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord. Acta Neuropathol. 2025;150(1):10.","journal-title":"Acta Neuropathol"},{"key":"572_CR116","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.773288","volume":"13","author":"C Figueroa-Romero","year":"2022","unstructured":"Figueroa-Romero C, Monteagudo A, Murdock BJ, Famie JP, Webber-Davis IF, Piecuch CE, et al. Tofacitinib suppresses natural killer cells in vitro and in vivo: implications for amyotrophic lateral sclerosis. Front Immunol. 2022;13:773288.","journal-title":"Front Immunol"},{"key":"572_CR117","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1662197","volume":"16","author":"LA Baird","year":"2025","unstructured":"Baird LA, Teener SJ, Webber-Davis IF, Carter AD, Huang F, Jang DG, et al. Tofacitinib extends survival in a mouse model of ALS through NK cell-independent mechanisms. Front Immunol. 2025;16:1662197.","journal-title":"Front Immunol"},{"issue":"10","key":"572_CR118","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1002\/acn3.70127","volume":"12","author":"BJ Murdock","year":"2025","unstructured":"Murdock BJ, Park J, Jang DG, Zhao B, Teener SJ, Webber-Davis IF, et al. In vitro modeling of natural killer cell cytotoxicity to inform personalized ALS therapeutics. Ann Clin Transl Neurol. 2025;12(10):2036\u201344.","journal-title":"Ann Clin Transl Neurol"},{"issue":"1","key":"572_CR119","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41392-021-00687-0","volume":"6","author":"D Li","year":"2021","unstructured":"Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 2021;6(1):291.","journal-title":"Signal Transduct Target Ther"},{"issue":"6","key":"572_CR120","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1111\/nan.12483","volume":"44","author":"S Lehmann","year":"2018","unstructured":"Lehmann S, Esch E, Hartmann P, Goswami A, Nikolin S, Weis J, et al. Expression profile of pattern recognition receptors in skeletal muscle of SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients. Neuropathol Appl Neurobiol. 2018;44(6):606\u201327.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"572_CR121","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1259742","volume":"17","author":"Y Shi","year":"2023","unstructured":"Shi Y, Zhu R. Analysis of damage-associated molecular patterns in amyotrophic lateral sclerosis based on ScRNA-seq and bulk RNA-seq data. Front Neurosci. 2023;17:1259742.","journal-title":"Front Neurosci"},{"issue":"7823","key":"572_CR122","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41586-020-2625-x","volume":"585","author":"ME McCauley","year":"2020","unstructured":"McCauley ME, O\u2019Rourke JG, Y\u00e1\u00f1ez A, Markman JL, Ho R, Wang X, et al. C9orf72 in myeloid cells suppresses STING-induced inflammation. Nature. 2020;585(7823):96\u2013101.","journal-title":"Nature"},{"issue":"1","key":"572_CR123","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s00401-024-02688-z","volume":"147","author":"C Marques","year":"2024","unstructured":"Marques C, Held A, Dorfman K, Sung J, Song C, Kavuturu AS, et al. Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathol. 2024;147(1):56.","journal-title":"Acta Neuropathol"},{"key":"572_CR124","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2025.101422","volume":"106","author":"Y Wu","year":"2025","unstructured":"Wu Y, Huang S, Sha Q, Yu J. Emerging and Re-emerging viruses as triggers of human endogenous retrovirus activation: Implications for aging and age-related pathologies. Mol Aspects Med. 2025;106:101422.","journal-title":"Mol Aspects Med"},{"issue":"1","key":"572_CR125","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00672-x","volume":"18","author":"Y Huang","year":"2023","unstructured":"Huang Y, Liu B, Sinha SC, Amin S, Gan L. Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders. Mol Neurodegener. 2023;18(1):79.","journal-title":"Mol Neurodegener"},{"issue":"7973","key":"572_CR126","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41586-023-06373-1","volume":"620","author":"MF Gulen","year":"2023","unstructured":"Gulen MF, Samson N, Keller A, Schwabenland M, Liu C, Gl\u00fcck S, et al. cGAS-STING drives ageing-related inflammation and neurodegeneration. Nature. 2023;620(7973):374\u201380.","journal-title":"Nature"},{"key":"572_CR127","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0310-z","volume":"12","author":"JY Lee","year":"2015","unstructured":"Lee JY, Lee JD, Phipps S, Noakes PG, Woodruff TM. Absence of toll-like receptor 4 (TLR4) extends survival in the hSOD1 G93A mouse model of amyotrophic lateral sclerosis. J Neuroinflammation. 2015;12:90.","journal-title":"J Neuroinflammation"},{"issue":"12","key":"572_CR128","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1084\/jem.20111313","volume":"208","author":"V Swarup","year":"2011","unstructured":"Swarup V, Phaneuf D, Dupr\u00e9 N, Petri S, Strong M, Kriz J, et al. Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor \u03baB-mediated pathogenic pathways. J Exp Med. 2011;208(12):2429\u201347.","journal-title":"J Exp Med"},{"issue":"6","key":"572_CR129","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1083\/jcb.200705046","volume":"179","author":"J Kang","year":"2007","unstructured":"Kang J, Rivest S. MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis. J Cell Biol. 2007;179(6):1219\u201330.","journal-title":"J Cell Biol"},{"issue":"1","key":"572_CR130","doi-asserted-by":"publisher","first-page":"9094","DOI":"10.1038\/s41598-017-09097-1","volume":"7","author":"Y Hu","year":"2017","unstructured":"Hu Y, Cao C, Qin XY, Yu Y, Yuan J, Zhao Y, et al. Increased peripheral blood inflammatory cytokine levels in amyotrophic lateral sclerosis: a meta-analysis study. Sci Rep. 2017;7(1):9094.","journal-title":"Sci Rep"},{"issue":"8","key":"572_CR131","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","volume":"19","author":"KV Swanson","year":"2019","unstructured":"Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19(8):477\u201389.","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"572_CR132","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1002\/glia.22891","volume":"63","author":"S Johann","year":"2015","unstructured":"Johann S, Heitzer M, Kanagaratnam M, Goswami A, Rizo T, Weis J, et al. NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients. Glia. 2015;63(12):2260\u201373.","journal-title":"Glia"},{"issue":"4","key":"572_CR133","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41423-025-01275-w","volume":"22","author":"W Xu","year":"2025","unstructured":"Xu W, Huang Y, Zhou R. NLRP3 inflammasome in neuroinflammation and central nervous system diseases. Cell Mol Immunol. 2025;22(4):341\u201355.","journal-title":"Cell Mol Immunol"},{"key":"572_CR134","doi-asserted-by":"publisher","first-page":"1190219","DOI":"10.3389\/fimmu.2023.1190219","volume":"14","author":"ML Cl\u00e9net","year":"2023","unstructured":"Cl\u00e9net ML, Keaney J, Gillet G, Valadas JS, Langlois J, Cardenas A, et al. Divergent functional outcomes of NLRP3 blockade downstream of multi-inflammasome activation: therapeutic implications for ALS. Front Immunol. 2023;14:1190219.","journal-title":"Front Immunol"},{"key":"572_CR135","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02122","volume":"9","author":"X Chen","year":"2018","unstructured":"Chen X, Hu Y, Cao Z, Liu Q, Cheng Y. Cerebrospinal fluid inflammatory cytokine aberrations in Alzheimer\u2019s disease, Parkinson\u2019s disease and amyotrophic lateral sclerosis: a systematic review and meta-analysis. Front Immunol. 2018;9:2122.","journal-title":"Front Immunol"},{"key":"572_CR136","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101202","volume":"65","author":"AG Wu","year":"2021","unstructured":"Wu AG, Zhou XG, Qiao G, Yu L, Tang Y, Yan L, et al. Targeting microglial autophagic degradation in NLRP3 inflammasome-mediated neurodegenerative diseases. Ageing Res Rev. 2021;65:101202.","journal-title":"Ageing Res Rev"},{"key":"572_CR137","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.expneurol.2017.03.014","volume":"292","author":"LT Rosenblum","year":"2017","unstructured":"Rosenblum LT, Shamamandri-Markandaiah S, Ghosh B, Foran E, Lepore AC, Pasinelli P, et al. Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS. Exp Neurol. 2017;292:145\u201353.","journal-title":"Exp Neurol"},{"issue":"11","key":"572_CR138","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1002\/glia.21218","volume":"59","author":"E Foran","year":"2011","unstructured":"Foran E, Bogush A, Goffredo M, Roncaglia P, Gustincich S, Pasinelli P, et al. Motor neuron impairment mediated by a sumoylated fragment of the glial glutamate transporter EAAT2. Glia. 2011;59(11):1719\u201331.","journal-title":"Glia"},{"issue":"1","key":"572_CR139","doi-asserted-by":"publisher","first-page":"7067","DOI":"10.1038\/s41467-021-27367-5","volume":"12","author":"J Du","year":"2021","unstructured":"Du J, Xiang Y, Liu H, Liu S, Kumar A, Xing C, et al. RIPK1 dephosphorylation and kinase activation by PPP1R3G\/PP1\u03b3 promote apoptosis and necroptosis. Nat Commun. 2021;12(1):7067.","journal-title":"Nat Commun"},{"issue":"4","key":"572_CR140","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.immuni.2025.02.024","volume":"58","author":"M Zelic","year":"2025","unstructured":"Zelic M, Blazier A, Pontarelli F, LaMorte M, Huang J, Tasdemir-Yilmaz OE, et al. Single-cell transcriptomic and functional studies identify glial state changes and a role for inflammatory RIPK1 signaling in ALS pathogenesis. Immunity. 2025;58(4):961-79.e8.","journal-title":"Immunity"},{"issue":"1","key":"572_CR141","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-67165-9","volume":"14","author":"C Femiano","year":"2024","unstructured":"Femiano C, Bruno A, Gilio L, Buttari F, Dolcetti E, Galifi G, et al. Inflammatory signature in amyotrophic lateral sclerosis predicting disease progression. Sci Rep. 2024;14(1):19796.","journal-title":"Sci Rep"},{"issue":"30","key":"572_CR142","doi-asserted-by":"publisher","first-page":"27620","DOI":"10.1074\/jbc.M303199200","volume":"278","author":"M Delgado","year":"2003","unstructured":"Delgado M. Inhibition of interferon (IFN) gamma-induced Jak-STAT1 activation in microglia by vasoactive intestinal peptide: inhibitory effect on CD40, IFN-induced protein-10, and inducible nitric-oxide synthase expression. J Biol Chem. 2003;278(30):27620\u20139.","journal-title":"J Biol Chem"},{"issue":"12","key":"572_CR143","doi-asserted-by":"publisher","first-page":"2674","DOI":"10.1002\/glia.23878","volume":"68","author":"J Zhang","year":"2020","unstructured":"Zhang J, He H, Qiao Y, Zhou T, He H, Yi S, et al. Priming of microglia with IFN-\u03b3 impairs adult hippocampal neurogenesis and leads to depression-like behaviors and cognitive defects. Glia. 2020;68(12):2674\u201392.","journal-title":"Glia"},{"issue":"9","key":"572_CR144","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.1172\/JCI62636","volume":"122","author":"O Butovsky","year":"2012","unstructured":"Butovsky O, Siddiqui S, Gabriely G, Lanser AJ, Dake B, Murugaiyan G, et al. Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest. 2012;122(9):3063\u201387.","journal-title":"J Clin Invest"},{"issue":"1","key":"572_CR145","doi-asserted-by":"publisher","first-page":"7053","DOI":"10.1038\/s41467-025-62351-3","volume":"16","author":"B N\u00f3gr\u00e1di","year":"2025","unstructured":"N\u00f3gr\u00e1di B, Moln\u00e1r K, Krist\u00f3f R, Horv\u00e1th O, Huang YT, Ridgway Z, et al. The CCL2-CCR2 axis drives neuromuscular denervation in amyotrophic lateral sclerosis. Nat Commun. 2025;16(1):7053.","journal-title":"Nat Commun"},{"key":"572_CR146","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107989","volume":"231","author":"MS Subbarayan","year":"2022","unstructured":"Subbarayan MS, Joly-Amado A, Bickford PC, Nash KR. CX3CL1\/CX3CR1 signaling targets for the treatment of neurodegenerative diseases. Pharmacol Ther. 2022;231:107989.","journal-title":"Pharmacol Ther"},{"issue":"5","key":"572_CR147","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096528","volume":"9","author":"A Lopez-Lopez","year":"2014","unstructured":"Lopez-Lopez A, Gamez J, Syriani E, Morales M, Salvado M, Rodr\u00edguez MJ, et al. CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis. PLoS ONE. 2014;9(5):e96528.","journal-title":"PLoS ONE"},{"issue":"11","key":"572_CR148","doi-asserted-by":"publisher","first-page":"2916","DOI":"10.3390\/biomedicines10112916","volume":"10","author":"A Sarikidi","year":"2022","unstructured":"Sarikidi A, Kefalakes E, Falk CS, Esser R, Ganser A, Thau-Habermann N, et al. Altered immunomodulatory responses in the CX3CL1\/CX3CR1 axis mediated by hMSCs in an early in vitro SOD1G93A model of ALS. Biomedicines (Basel).\u00a02022;10(11):2916.","journal-title":"Biomedicines (Basel)"},{"issue":"3","key":"572_CR149","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.nbd.2011.01.002","volume":"42","author":"M Sta","year":"2011","unstructured":"Sta M, Sylva-Steenland RM, Casula M, de Jong JM, Troost D, Aronica E, et al. Innate and adaptive immunity in amyotrophic lateral sclerosis: evidence of complement activation. Neurobiol Dis. 2011;42(3):211\u201320.","journal-title":"Neurobiol Dis"},{"key":"572_CR150","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.nbd.2019.03.003","volume":"127","author":"SE Parker","year":"2019","unstructured":"Parker SE, Hanton AM, Stefanou SN, Noakes PG, Woodruff TM, Lee JD. Revisiting the role of the innate immune complement system in ALS. Neurobiol Dis. 2019;127:223\u201332.","journal-title":"Neurobiol Dis"},{"issue":"1\u20132","key":"572_CR151","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.jneuroim.2011.03.011","volume":"235","author":"B Heurich","year":"2011","unstructured":"Heurich B, El Idrissi NB, Donev RM, Petri S, Claus P, Neal J, et al. Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis. J Neuroimmunol. 2011;235(1\u20132):104\u20139.","journal-title":"J Neuroimmunol"},{"issue":"1\u20132","key":"572_CR152","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.jneuroim.2014.09.005","volume":"276","author":"S Mantovani","year":"2014","unstructured":"Mantovani S, Gordon R, Macmaw JK, Pfluger CM, Henderson RD, Noakes PG, et al. Elevation of the terminal complement activation products C5a and C5b\u20139 in ALS patient blood. J Neuroimmunol. 2014;276(1\u20132):213\u20138.","journal-title":"J Neuroimmunol"},{"issue":"1","key":"572_CR153","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41583-018-0093-1","volume":"20","author":"J Yuan","year":"2019","unstructured":"Yuan J, Amin P, Ofengeim D. Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases. Nat Rev Neurosci. 2019;20(1):19\u201333.","journal-title":"Nat Rev Neurosci"},{"issue":"8","key":"572_CR154","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/s41573-020-0071-y","volume":"19","author":"L Mifflin","year":"2020","unstructured":"Mifflin L, Ofengeim D, Yuan J. Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat Rev Drug Discov. 2020;19(8):553\u201371.","journal-title":"Nat Rev Drug Discov"},{"issue":"6","key":"572_CR155","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1016\/j.cell.2018.07.041","volume":"174","author":"D Xu","year":"2018","unstructured":"Xu D, Jin T, Zhu H, Chen H, Ofengeim D, Zou C, et al. TBK1 suppresses RIPK1-driven apoptosis and inflammation during development and in aging. Cell. 2018;174(6):1477-91.e19.","journal-title":"Cell"},{"issue":"6299","key":"572_CR156","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1126\/science.aaf6803","volume":"353","author":"Y Ito","year":"2016","unstructured":"Ito Y, Ofengeim D, Najafov A, Das S, Saberi S, Li Y, et al. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science. 2016;353(6299):603\u20138.","journal-title":"Science"},{"issue":"13","key":"572_CR157","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025102118","volume":"118","author":"L Mifflin","year":"2021","unstructured":"Mifflin L, Hu Z, Dufort C, Hession CC, Walker AJ, Niu K, et al. A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2021;118(13):e2025102118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"572_CR158","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.976435","volume":"13","author":"L Chen","year":"2022","unstructured":"Chen L, Zhang X, Ou Y, Liu M, Yu D, Song Z, et al. Advances in RIPK1 kinase inhibitors. Front Pharmacol. 2022;13:976435.","journal-title":"Front Pharmacol"},{"issue":"1","key":"572_CR159","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1038\/s41467-019-09690-0","volume":"10","author":"Y Dondelinger","year":"2019","unstructured":"Dondelinger Y, Delanghe T, Priem D, Wynosky-Dolfi MA, Sorobetea D, Rojas-Rivera D, et al. Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation. Nat Commun. 2019;10(1):1729.","journal-title":"Nat Commun"},{"issue":"17","key":"572_CR160","doi-asserted-by":"publisher","first-page":"4447","DOI":"10.1016\/j.cell.2021.07.026","volume":"184","author":"J Taft","year":"2021","unstructured":"Taft J, Markson M, Legarda D, Patel R, Chan M, Malle L, et al. Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death. Cell. 2021;184(17):4447-63.e20.","journal-title":"Cell"},{"issue":"10","key":"572_CR161","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1212\/01.WNL.0000125321.92112.7E","volume":"62","author":"PH Gordon","year":"2004","unstructured":"Gordon PH, Moore DH, Gelinas DF, Qualls C, Meister ME, Werner J, et al. Placebo-controlled phase I\/II studies of minocycline in amyotrophic lateral sclerosis. Neurology. 2004;62(10):1845\u20137.","journal-title":"Neurology"},{"issue":"7\u20138","key":"572_CR162","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1080\/21678421.2020.1788093","volume":"21","author":"MA Van Es","year":"2020","unstructured":"Van Es MA, Van Eijk R, Bunte TM, Van Den Berg LH. A placebo-controlled trial to investigate the safety and efficacy of Penicillin G\/Hydrocortisone in patients with ALS (PHALS trial). Amyotroph Lateral Scler Frontotemporal Degener. 2020;21(7\u20138):584\u201392.","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"572_CR163","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1659216","volume":"17","author":"H Zhang","year":"2025","unstructured":"Zhang H, He Z, Yin C, Yang S, Li J, Lin H, et al. STING-mediated neuroinflammation: a therapeutic target in neurodegenerative diseases. Front Aging Neurosci. 2025;17:1659216.","journal-title":"Front Aging Neurosci"},{"issue":"11","key":"572_CR164","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1038\/s43587-024-00740-x","volume":"4","author":"S Paganoni","year":"2024","unstructured":"Paganoni S, Harkey B, Giacomelli E, Cudkowicz M, HEALEY ALS Platform Trial Study Group. Lessons from the HEALEY adaptive platform trial in amyotrophic lateral sclerosis. Nat Aging. 2024;4(11):1512\u20135.","journal-title":"Nat Aging"},{"issue":"2","key":"572_CR165","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1093\/cei\/uxac105","volume":"211","author":"F Harris","year":"2023","unstructured":"Harris F, Berdugo YA, Tree T. IL-2-based approaches to treg enhancement. Clin Exp Immunol. 2023;211(2):149\u201363.","journal-title":"Clin Exp Immunol"},{"key":"572_CR166","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102844","volume":"59","author":"W Camu","year":"2020","unstructured":"Camu W, Mickunas M, Veyrune JL, Payan C, Garlanda C, Locati M, et al. Repeated 5-day cycles of low dose aldesleukin in amyotrophic lateral sclerosis (IMODALS): a phase 2a randomised, double-blind, placebo-controlled trial. EBioMedicine. 2020;59:102844.","journal-title":"EBioMedicine"},{"issue":"10492","key":"572_CR167","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1016\/S0140-6736(25)00262-4","volume":"405","author":"G Bensimon","year":"2025","unstructured":"Bensimon G, Leigh PN, Tree T, Malaspina A, Payan CA, Pham HP, et al. Efficacy and safety of low-dose IL-2 as an add-on therapy to riluzole (MIROCALS): a phase 2b, double-blind, randomised, placebo-controlled trial. Lancet. 2025;405(10492):1837\u201350.","journal-title":"Lancet"},{"issue":"1","key":"572_CR168","doi-asserted-by":"publisher","first-page":"4970","DOI":"10.1038\/s41467-023-40734-8","volume":"14","author":"J Mandrioli","year":"2023","unstructured":"Mandrioli J, D\u2019Amico R, Zucchi E, De Biasi S, Banchelli F, Martinelli I, et al. Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis. Nat Commun. 2023;14(1):4970.","journal-title":"Nat Commun"},{"issue":"6","key":"572_CR169","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200019","volume":"9","author":"JR Thonhoff","year":"2022","unstructured":"Thonhoff JR, Berry JD, Macklin EA, Beers DR, Mendoza PA, Zhao W, et al. Combined regulatory T-lymphocyte and IL-2 treatment is safe, tolerable, and biologically active for 1 year in persons with amyotrophic lateral sclerosis. Neurol Neuroimmunol Neuroinflamm. 2022;9(6):e200019.","journal-title":"Neurol Neuroimmunol Neuroinflamm."},{"issue":"17","key":"572_CR170","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1212\/01.wnl.0000327668.43541.22","volume":"71","author":"SH Appel","year":"2008","unstructured":"Appel SH, Engelhardt JI, Henkel JS, Siklos L, Beers DR, Yen AA, et al. Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology. 2008;71(17):1326\u201334.","journal-title":"Neurology"},{"issue":"10","key":"572_CR171","doi-asserted-by":"publisher","first-page":"5337","DOI":"10.1007\/s00415-022-11185-w","volume":"269","author":"C Lunetta","year":"2022","unstructured":"Lunetta C, Lizio A, Cabona C, Gerardi F, Sansone VA, Corbo M, et al. A phase I\/IIa clinical trial of autologous hematopoietic stem cell transplantation in amyotrophic lateral sclerosis. J Neurol. 2022;269(10):5337\u201346.","journal-title":"J Neurol"},{"issue":"3","key":"572_CR172","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1002\/ana.25302","volume":"84","author":"KW Oh","year":"2018","unstructured":"Oh KW, Noh MY, Kwon MS, Kim HY, Oh SI, Park J, et al. Repeated intrathecal mesenchymal stem cells for amyotrophic lateral sclerosis. Ann Neurol. 2018;84(3):361\u201373.","journal-title":"Ann Neurol"},{"issue":"3","key":"572_CR173","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/mus.27472","volume":"65","author":"ME Cudkowicz","year":"2022","unstructured":"Cudkowicz ME, Lindborg SR, Goyal NA, Miller RG, Burford MJ, Berry JD, et al. A randomized placebo-controlled phase 3 study of mesenchymal stem cells induced to secrete high levels of neurotrophic factors in amyotrophic lateral sclerosis. Muscle Nerve. 2022;65(3):291\u2013302.","journal-title":"Muscle Nerve"},{"issue":"10","key":"572_CR174","first-page":"1307","volume":"12","author":"J You","year":"2023","unstructured":"You J, Youssef M, Santos JR, Lee J, Park J. Microglia and astrocytes in amyotrophic lateral sclerosis: disease-associated states, pathological roles, and therapeutic potential. Biology (Basel).\u00a02023;12(10):1307.","journal-title":"Biology (Basel)"},{"issue":"1","key":"572_CR175","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/s41467-025-56124-1","volume":"16","author":"R Martins-Ferreira","year":"2025","unstructured":"Martins-Ferreira R, Calafell-Segura J, Leal B, Rodr\u00edguez-Ubreva J, Mart\u00ednez-Saez E, Mereu E, et al. The human microglia atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions. Nat Commun. 2025;16(1):739.","journal-title":"Nat Commun"},{"issue":"21","key":"572_CR176","doi-asserted-by":"publisher","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","volume":"110","author":"RC Paolicelli","year":"2022","unstructured":"Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, et al. Microglia states and nomenclature: a field at its crossroads. Neuron. 2022;110(21):3458\u201383.","journal-title":"Neuron"},{"issue":"1","key":"572_CR177","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0620-9","volume":"13","author":"E Trias","year":"2016","unstructured":"Trias E, Ibarburu S, Barreto-N\u00fa\u00f1ez R, Babdor J, Maciel TT, Guillo M, et al. Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. J Neuroinflammation. 2016;13(1):177.","journal-title":"J Neuroinflammation"},{"issue":"2","key":"572_CR178","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.neuron.2014.02.040","volume":"82","author":"MR Elmore","year":"2014","unstructured":"Elmore MR, Najafi AR, Koike MA, Dagher NN, Spangenberg EE, Rice RA, et al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron. 2014;82(2):380\u201397.","journal-title":"Neuron"},{"issue":"1","key":"572_CR179","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.1038\/s41467-019-11674-z","volume":"10","author":"E Spangenberg","year":"2019","unstructured":"Spangenberg E, Severson PL, Hohsfield LA, Crapser J, Zhang J, Burton EA, et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer\u2019s disease model. Nat Commun. 2019;10(1):3758.","journal-title":"Nat Commun"},{"key":"572_CR180","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2024.1352790","volume":"18","author":"R Boland","year":"2024","unstructured":"Boland R, Kokiko-Cochran ON. Deplete and repeat: microglial CSF1R inhibition and traumatic brain injury. Front Cell Neurosci. 2024;18:1352790.","journal-title":"Front Cell Neurosci"},{"issue":"2","key":"572_CR181","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200527","volume":"13","author":"Y Che","year":"2026","unstructured":"Che Y, Yu Z, Ji S, Yang D. Decoding TREM2 signaling pathways: linking macrophage glycolysis to inflammatory diseases in the CNS. Neurol Neuroimmunol Neuroinflamm. 2026;13(2):e200527.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"6","key":"572_CR182","doi-asserted-by":"publisher","DOI":"10.1002\/alz.084622","volume":"20","author":"C Mirescu","year":"2024","unstructured":"Mirescu C. Characterization of the first TREM2 small molecule agonist, VG -3927, for clinical development in Alzheimer\u2019s disease. Alzheimers Dement. 2024;20(6):e084622.","journal-title":"Alzheimers Dement"},{"issue":"9","key":"572_CR183","doi-asserted-by":"publisher","first-page":"3250","DOI":"10.1172\/JCI90607","volume":"127","author":"D Lall","year":"2017","unstructured":"Lall D, Baloh RH. Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia. J Clin Invest. 2017;127(9):3250\u20138.","journal-title":"J Clin Invest"},{"issue":"4","key":"572_CR184","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1001\/jamaneurol.2013.6237","volume":"71","author":"J Cady","year":"2014","unstructured":"Cady J, Koval ED, Benitez BA, Zaidman C, Jockel-Balsarotti J, Allred P, et al. TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis. JAMA Neurol. 2014;71(4):449\u201353.","journal-title":"JAMA Neurol"},{"issue":"1","key":"572_CR185","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/s42003-025-07790-w","volume":"8","author":"JY Hiew","year":"2025","unstructured":"Hiew JY, Lim YS, Liu H, Ng CS. Integrated transcriptomic profiling reveals a STING-mediated Type II Interferon signature in SOD1-mutant amyotrophic lateral sclerosis models. Commun Biol. 2025;8(1):347.","journal-title":"Commun Biol"},{"issue":"52","key":"572_CR186","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2308853120","volume":"120","author":"F Qin","year":"2023","unstructured":"Qin F, Cai B, Cao R, Bai X, Yuan J, Zhang Y, et al. Listerin promotes cGAS protein degradation through the ESCRT pathway to negatively regulate cGAS-mediated immune response. Proc Natl Acad Sci U S A. 2023;120(52):e2308853120.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"572_CR187","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1002\/mus.27339","volume":"64","author":"C Milligan","year":"2021","unstructured":"Milligan C, Atassi N, Babu S, Barohn RJ, Caress JB, Cudkowicz ME, et al. Tocilizumab is safe and tolerable and reduces C-reactive protein concentrations in the plasma and cerebrospinal fluid of ALS patients. Muscle Nerve. 2021;64(3):309\u201320.","journal-title":"Muscle Nerve"},{"issue":"4","key":"572_CR188","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153399","volume":"11","author":"Y Han","year":"2016","unstructured":"Han Y, Ripley B, Serada S, Naka T, Fujimoto M. Interleukin-6 deficiency does not affect motor neuron disease caused by superoxide dismutase 1 mutation. PLoS ONE. 2016;11(4):e0153399.","journal-title":"PLoS ONE"},{"issue":"1","key":"572_CR189","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1589-y","volume":"16","author":"JH Jara","year":"2019","unstructured":"Jara JH, Gautam M, Kocak N, Xie EF, Mao Q, Bigio EH, et al. MCP1-CCR2 and neuroinflammation in the ALS motor cortex with TDP-43 pathology. J Neuroinflammation. 2019;16(1):196.","journal-title":"J Neuroinflammation"},{"issue":"6756","key":"572_CR190","doi-asserted-by":"publisher","DOI":"10.1126\/science.adr1015","volume":"389","author":"J Wu","year":"2025","unstructured":"Wu J, Wang Y, Li X, Ouyang P, Cai Y, He Y, et al. Microglia replacement halts the progression of microgliopathy in mice and humans. Science. 2025;389(6756):eadr1015.","journal-title":"Science"},{"issue":"8","key":"572_CR191","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.3390\/genes14081658","volume":"14","author":"F De Marchi","year":"2023","unstructured":"De Marchi F, Tondo G, Corrado L, Menegon F, Aprile D, Anselmi M, et al. Neuroinflammatory pathways in the ALS-FTD continuum: a focus on genetic variants. Genes (Basel).\u00a02023;14(8):1658.","journal-title":"Genes (Basel)"},{"issue":"4","key":"572_CR192","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1136\/jnnp-2021-327503","volume":"93","author":"M Dreger","year":"2022","unstructured":"Dreger M, Steinbach R, Otto M, Turner MR, Grosskreutz J. Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2022;93(4):422\u201335.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"6","key":"572_CR193","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1007\/s10072-024-07301-5","volume":"45","author":"A Xu","year":"2024","unstructured":"Xu A, Luo Y, Tang Y, Yang F, Gao X, Qiao G, et al. Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis. Neurol Sci. 2024;45(6):2489\u2013503.","journal-title":"Neurol Sci"},{"issue":"3","key":"572_CR194","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1136\/jnnp-2017-317138","volume":"89","author":"P Steinacker","year":"2018","unstructured":"Steinacker P, Verde F, Fang L, Feneberg E, Oeckl P, Roeber S, et al. Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression. J Neurol Neurosurg Psychiatry. 2018;89(3):239\u201347.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"3","key":"572_CR195","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000697","volume":"7","author":"MN Olesen","year":"2020","unstructured":"Olesen MN, Wuolikainen A, Nilsson AC, Wirenfeldt M, Forsberg K, Madsen JS, et al. Inflammatory profiles relate to survival in subtypes of amyotrophic lateral sclerosis. Neurol Neuroimmunol Neuroinflamm. 2020;7(3):e697.","journal-title":"Neurol Neuroimmunol Neuroinflamm."},{"issue":"10","key":"572_CR196","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004469","volume":"21","author":"S Perrin","year":"2024","unstructured":"Perrin S, Ladha S, Maragakis N, Rivner MH, Katz J, Genge A, et al. Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: a phase 2a clinical trial. PLoS Med. 2024;21(10):e1004469.","journal-title":"PLoS Med"},{"issue":"6","key":"572_CR197","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1001\/jamaneurol.2016.6179","volume":"74","author":"C Lunetta","year":"2017","unstructured":"Lunetta C, Lizio A, Maestri E, Sansone VA, Mora G, Miller RG, et al. Serum C-reactive protein as a prognostic biomarker in amyotrophic lateral sclerosis. JAMA Neurol. 2017;74(6):660\u20137.","journal-title":"JAMA Neurol"},{"issue":"1","key":"572_CR198","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-041479","volume":"11","author":"S Vucic","year":"2021","unstructured":"Vucic S, Kiernan MC, Menon P, Huynh W, Rynders A, Ho KS, et al. Study protocol of RESCUE-ALS: a phase 2, randomised, double-blind, placebo-controlled study in early symptomatic amyotrophic lateral sclerosis patients to assess bioenergetic catalysis with CNM-Au8 as a mechanism to slow disease progression. BMJ Open. 2021;11(1):e041479.","journal-title":"BMJ Open"},{"key":"572_CR199","unstructured":"Writing committee for the HEALEY ALS platform trial, Berry JD, Maragakis NJ, Macklin EA, Chibnik LB, Quintana M, et al. CNM-Au8 in amyotrophic lateral sclerosis: the HEALEY ALS platform trial. JAMA. 2025."},{"issue":"12","key":"572_CR200","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","volume":"387","author":"TM Miller","year":"2022","unstructured":"Miller TM, Cudkowicz ME, Genge A, Shaw PJ, Sobue G, Bucelli RC, et al. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med. 2022;387(12):1099\u2013110.","journal-title":"N Engl J Med"},{"issue":"3","key":"572_CR201","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/cei.13660","volume":"206","author":"S Amor","year":"2021","unstructured":"Amor S, Nutma E, Marzin M, Puentes F. Imaging immunological processes from blood to brain in amyotrophic lateral sclerosis. Clin Exp Immunol. 2021;206(3):301\u201313.","journal-title":"Clin Exp Immunol"},{"issue":"2","key":"572_CR202","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.apsb.2020.08.006","volume":"11","author":"L Zhang","year":"2021","unstructured":"Zhang L, Hu K, Shao T, Hou L, Zhang S, Ye W, et al. Recent developments on PET radiotracers for TSPO and their applications in neuroimaging. Acta Pharm Sin B. 2021;11(2):373\u201393.","journal-title":"Acta Pharm Sin B"},{"issue":"1","key":"572_CR203","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s41467-022-35494-w","volume":"14","author":"J Eshima","year":"2023","unstructured":"Eshima J, O\u2019Connor SA, Marschall E, Bowser R, Plaisier CL, Smith BS. Molecular subtypes of ALS are associated with differences in patient prognosis. Nat Commun. 2023;14(1):95.","journal-title":"Nat Commun"},{"issue":"3","key":"572_CR204","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115402","volume":"44","author":"K O\u2019Neill","year":"2025","unstructured":"O\u2019Neill K, Shaw R, Bolger I, Tam OH, Phatnani H, et al. ALS molecular subtypes are a combination of cellular and pathological features learned by deep multiomics classifiers. Cell Rep. 2025;44(3):115402.","journal-title":"Cell Rep"},{"issue":"9643","key":"572_CR205","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/S0140-6736(08)61452-X","volume":"372","author":"GP Anderson","year":"2008","unstructured":"Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008;372(9643):1107\u201319.","journal-title":"Lancet"},{"issue":"Suppl 1","key":"572_CR206","doi-asserted-by":"publisher","first-page":"S42","DOI":"10.1016\/S0140-6736(15)60357-9","volume":"385","author":"T Hinks","year":"2015","unstructured":"Hinks T, Zhou X, Staples K, Dimitrov B, Manta A, Petrossian T, et al. Multidimensional endotypes of asthma: topological data analysis of cross-sectional clinical, pathological, and immunological data. Lancet. 2015;385(Suppl 1):S42.","journal-title":"Lancet"},{"issue":"2","key":"572_CR207","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1093\/braincomms\/fcaa124","volume":"2","author":"LC B\u00e9land","year":"2020","unstructured":"B\u00e9land LC, Markovinovic A, Jakovac H, De Marchi F, Bilic E, Mazzini L, et al. Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient immune responses. Brain Commun. 2020;2(2):124.","journal-title":"Brain Commun."},{"issue":"Pt 6","key":"572_CR208","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1093\/brain\/awn071","volume":"131","author":"S Vucic","year":"2008","unstructured":"Vucic S, Nicholson GA, Kiernan MC. Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain. 2008;131(Pt 6):1540\u201350.","journal-title":"Brain"},{"issue":"4","key":"572_CR209","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1002\/ana.27305","volume":"98","author":"F Ranieri","year":"2025","unstructured":"Ranieri F, Senerchia G, Bonan L, Casali S, Cabona C, Cantone M, et al. Cortical excitability as a prognostic and phenotypic stratification biomarker in amyotrophic lateral sclerosis. Ann Neurol. 2025;98(4):801\u201313.","journal-title":"Ann Neurol"},{"issue":"8","key":"572_CR210","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2025.100673","volume":"6","author":"BJ Murdock","year":"2025","unstructured":"Murdock BJ, Zhao B, Webber-Davis IF, Teener SJ, Pawlowski KD, Famie JP, et al. Early immune system changes in amyotrophic lateral sclerosis correlate with later disease progression. Med. 2025;6(8):100673.","journal-title":"Med"},{"issue":"9","key":"572_CR211","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1111\/j.1755-5949.2012.00358.x","volume":"18","author":"Q Kong","year":"2012","unstructured":"Kong Q, Carothers S, Chang Y, Glenn Lin CL. The importance of preclinical trial timing - a potential reason for the disconnect between mouse studies and human clinical trials in ALS. CNS Neurosci Ther. 2012;18(9):791\u20133.","journal-title":"CNS Neurosci Ther"},{"issue":"5-6","key":"572_CR212","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1080\/21678421.2019.1587634","volume":"20","author":"M Benatar","year":"2019","unstructured":"Benatar M, Turner MR, Wuu J. Defining pre-symptomatic amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2019;20(5\u20136):303\u20139.","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"issue":"4","key":"572_CR213","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1007\/s13311-022-01271-2","volume":"19","author":"CN Fournier","year":"2022","unstructured":"Fournier CN. Considerations for amyotrophic lateral sclerosis (ALS) llinical trial design. Neurotherapeutics. 2022;19(4):1180\u201392.","journal-title":"Neurotherapeutics"},{"key":"572_CR214","doi-asserted-by":"publisher","first-page":"7034143","DOI":"10.1155\/2017\/7034143","volume":"2017","author":"AR Santiago","year":"2017","unstructured":"Santiago AR, Bernardino L, Agudo-Barriuso M, Gon\u00e7alves J. Microglia in health and disease: a double-edged sword. Mediators Inflamm. 2017:2017:7034143.","journal-title":"Mediators Inflamm"},{"key":"572_CR215","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.815347","volume":"14","author":"S Guo","year":"2022","unstructured":"Guo S, Wang H, Yin Y. Microglia polarization from M1 to M2 in neurodegenerative diseases. Front Aging Neurosci. 2022;14:815347.","journal-title":"Front Aging Neurosci"},{"issue":"6","key":"572_CR216","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41582-021-00487-8","volume":"17","author":"BF Vahsen","year":"2021","unstructured":"Vahsen BF, Gray E, Thompson AG, Ansorge O, Anthony DC, Cowley SA, et al. Non-neuronal cells in amyotrophic lateral sclerosis - from pathogenesis to biomarkers. Nat Rev Neurol. 2021;17(6):333\u201348.","journal-title":"Nat Rev Neurol"},{"issue":"8","key":"572_CR217","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9081784","volume":"9","author":"G Arru","year":"2021","unstructured":"Arru G, Galleri G, Deiana GA, Zarbo IR, Sechi E, Bo M, et al. HERV-K modulates the immune response in ALS patients. Microorganisms. 2021;9(8):115402.","journal-title":"Microorganisms."},{"issue":"7","key":"572_CR218","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.3390\/jpm12071071","volume":"12","author":"H Alarcan","year":"2022","unstructured":"Alarcan H, Al Ojaimi Y, Lanznaster D, Escoffre JM, Corcia P, Vourch P, et al. Taking advantages of blood-brain or spinal cord barrier alterations or restoring them to optimize therapy in ALS. J Pers Med. 2022;12(7):1071.","journal-title":"J Pers Med."},{"issue":"1","key":"572_CR219","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12987-024-00565-1","volume":"21","author":"JM Wasielewska","year":"2024","unstructured":"Wasielewska JM, Chaves J, Cabral-da-Silva MC, Pecoraro M, Viljoen SJ, Nguyen TH, et al. A patient-derived amyotrophic lateral sclerosis blood-brain barrier model for focused ultrasound-mediated anti-TDP-43 antibody delivery. Fluids Barriers CNS. 2024;21(1):65.","journal-title":"Fluids Barriers CNS"},{"issue":"3","key":"572_CR220","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s11095-022-03185-2","volume":"39","author":"JM Wasielewska","year":"2022","unstructured":"Wasielewska JM, White AR. Focused ultrasound-mediated drug delivery in humans - a path towards translation in neurodegenerative diseases. Pharm Res. 2022;39(3):427\u201339.","journal-title":"Pharm Res"},{"issue":"7","key":"572_CR221","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1093\/brain\/awac394","volume":"146","author":"M Benatar","year":"2023","unstructured":"Benatar M, Wuu J, Turner MR. Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal. Brain. 2023;146(7):2711\u20136.","journal-title":"Brain"}],"container-title":["Translational Neurodegeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40035-026-00572-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40035-026-00572-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40035-026-00572-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T04:02:06Z","timestamp":1787544126000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40035-026-00572-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":221,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["572"],"URL":"https:\/\/doi.org\/10.1186\/s40035-026-00572-2","relation":{},"ISSN":["2047-9158"],"issn-type":[{"value":"2047-9158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"assertion":[{"value":"2 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent for participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"40"}}