{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:59:33Z","timestamp":1790247573205,"version":"4.1.0"},"reference-count":269,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with limited therapeutic options, highlighting the need for multi-target interventions. Traditional Chinese botanical medicine (TCBM) interventions have attracted increasing attention as potential multi-target pharmacological candidates for ALS. In addition, a separate body of evidence derived from selected plant-derived bioactive compounds directly investigated in ALS-specific models provides complementary mechanistic insights into ALS-related pathways. However, the pharmacological mechanisms and translational potential of these two distinct evidence categories remain insufficiently summarized. This review systematically summarizes ALS-related pathological mechanisms and the molecular actions reported within these two distinct evidence categories, together with translational challenges and future research directions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A structured literature search was conducted in PubMed, Web of Science, and ScienceDirect up to May 2026. A total of 198 publications were retained, including 48 ALS-specific original intervention studies forming the core pharmacological evidence set.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ALS involves interconnected pathological processes, including neuroinflammation, oxidative stress, mitochondrial dysfunction, impaired proteostasis, excitotoxicity, and neuromuscular junction injury. Evidence across these two categories suggests modulation of multiple ALS-related pathological processes. Reported effects include regulation of inflammatory signaling, enhancement of Nrf2-mediated antioxidant responses, improvement of PGC-1\u03b1\/MFN2-associated mitochondrial homeostasis, and promotion of protein clearance pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these distinct but complementary evidence categories highlight the potential for multi-target modulation of ALS-related pathology. However, current evidence remains predominantly preclinical, and clinical efficacy and translational feasibility require further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1918967","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:04:08Z","timestamp":1790244248000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Traditional Chinese botanical medicines and plant-derived bioactive compounds in amyotrophic lateral sclerosis: mechanistic evidence, translational challenges, and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengfan","family":"Li","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghao","family":"Li","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Surgery-Transplant Surgery, Johns Hopkins University School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Oncology Center-Breast and GYN Malignancies, Johns Hopkins University School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimeng","family":"Lv","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjing","family":"Shi","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoteng","family":"Ma","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Guan","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine Affiliated Hospital","place":["Jinan, Shandong, China"]},{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Teng","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]},{"name":"Shandong University of Traditional Chinese Medicine Affiliated Hospital","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"969","DOI":"10.3390\/antiox13080969","article-title":"The bioactive gamma-oryzanol from oryza sativa L. Promotes neuronal differentiation in different in vitro and in vivo models","volume":"13","author":"Abate","year":"2024","journal-title":"Antioxidants"},{"key":"B2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.bioorg.2018.10.017","article-title":"Dual effects of isoflavonoids from Pueraria lobata roots on estrogenic activity and anti-proliferation of MCF-7 human breast carcinoma cells","volume":"83","author":"Ahn","year":"2019","journal-title":"Bioorg Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.bbrc.2016.10.134","article-title":"Imbalance of mitochondrial dynamics in drosophila models of amyotrophic lateral sclerosis","volume":"481","author":"Altanbyek","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"5587","DOI":"10.3390\/ijms25115587","article-title":"Revisiting glutamate excitotoxicity in amyotrophic lateral sclerosis and age-related neurodegeneration","volume":"25","author":"Arnold","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.jep.2005.02.002","article-title":"Larrea tridentata (creosote bush), an abundant plant of mexican and US-American deserts and its metabolite nordihydroguaiaretic acid","volume":"98","author":"Arteaga","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/2909168","article-title":"Molecular mechanisms of neurodegeneration related to C9orf72 hexanucleotide repeat expansion","volume":"2019","author":"Babi\u0107 Leko","year":"2019","journal-title":"Behav. Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2998","DOI":"10.1093\/brain\/awae109","article-title":"Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial","volume":"147","author":"Babu","year":"2024","journal-title":"Brain"},{"key":"B8","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1080\/17582024.2025.2598227","article-title":"Tetramethylpyrazine nitrone: a multifaceted neuroprotective agent in neurodegenerative disorders","volume":"16","author":"Bahbah","year":"2026","journal-title":"Neurodegener. Dis. Manag."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1042\/BST20130186","article-title":"The role of TDP-43 in the pathogenesis of ALS and FTLD","volume":"41","author":"Baralle","year":"2013","journal-title":"Biochem. Soc. Trans."},{"key":"B10","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.freeradbiomed.2009.11.018","article-title":"Oxidative stress in ALS: key role in motor neuron injury and therapeutic target","volume":"48","author":"Barber","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"110598","DOI":"10.1016\/j.celrep.2022.110598","article-title":"ALS-associated KIF5A mutations abolish autoinhibition resulting in a toxic gain of function","volume":"39","author":"Baron","year":"2022","journal-title":"Cell Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3306","DOI":"10.1080\/15548627.2021.1872189","article-title":"C9orf72 ALS-FTD: recent evidence for dysregulation of the autophagy-lysosome pathway at multiple levels","volume":"17","author":"Beckers","year":"2021","journal-title":"Autophagy"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/j.1755-5949.2009.00116.x","article-title":"A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade? neural mechanisms of action and clinical efficiency of riluzole in treating ALS","volume":"17","author":"Bellingham","year":"2011","journal-title":"CNS Neurosci. Ther."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1093\/brain\/awac394","article-title":"Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal","volume":"146","author":"Benatar","year":"2023","journal-title":"Brain"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/21678421.2013.838969","article-title":"Predicting success: optimizing phase II ALS trials for the transition to phase III","volume":"15","author":"Berry","year":"2014","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"B16","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1001\/archneur.1984.04050170073021","article-title":"Quantitative axon terminal and end-plate morphology in amyotrophic lateral sclerosis","volume":"41","author":"Bjornskov","year":"1984","journal-title":"Arch. Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1096\/fj.14-269043","article-title":"Translating dosages from animal models to human clinical trials\u2014revisiting body surface area scaling","volume":"29","author":"Blanchard","year":"2015","journal-title":"FASEB J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.neuron.2006.09.018","article-title":"ALS: a disease of motor neurons and their nonneuronal neighbors","volume":"52","author":"Boill\u00e9e","year":"2006","journal-title":"Neuron"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4552","DOI":"10.3390\/ijms20184552","article-title":"Enhanced function and overexpression of metabotropic glutamate receptors 1 and 5 in the spinal cord of the SOD1G93A mouse model of amyotrophic lateral sclerosis during disease progression","volume":"20","author":"Bonifacino","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1164251","DOI":"10.3389\/fnins.2023.1164251","article-title":"Reduced levels of ALS gene DCTN1 induce motor defects in drosophila","volume":"17","author":"Borg","year":"2023","journal-title":"Front. Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.expneurol.2008.06.010","article-title":"Nordihydroguaiaretic acid increases glutamate uptake in vitro and in vivo: therapeutic implications for amyotrophic lateral sclerosis","volume":"213","author":"Boston-Howes","year":"2008","journal-title":"Exp. Neurol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1136\/jnnp-2023-332106","article-title":"Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial","volume":"95","author":"Bowser","year":"2024","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B23","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41586-022-04436-3","article-title":"TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A","volume":"603","author":"Brown","year":"2022","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1002\/acn3.179","article-title":"Endplate denervation correlates with nogo-a muscle expression in amyotrophic lateral sclerosis patients","volume":"2","author":"Bruneteau","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1007\/s00401-019-01964-7","article-title":"Disrupted neuronal trafficking in amyotrophic lateral sclerosis","volume":"137","author":"Burk","year":"2019","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"579","DOI":"10.3390\/antiox11030579","article-title":"Combined treatment with bojungikgi-tang and riluzole regulates muscle metabolism and dysfunction in the hSOD1G93A mouse model","volume":"11","author":"Cai","year":"2022","journal-title":"Antioxidants"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1007\/s12035-018-1236-0","article-title":"Bojungikgi-tang improves muscle and spinal cord function in an amyotrophic lateral sclerosis model","volume":"56","author":"Cai","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"BSR20190243","DOI":"10.1042\/BSR20190243","article-title":"Allicin alleviates lead-induced hematopoietic stem cell aging by up-regulating PKM2","volume":"39","author":"Cai","year":"2019","journal-title":"Biosci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1097\/WCO.0000000000001279","article-title":"Neuroinflammation in amyotrophic lateral sclerosis: pathogenic insights and therapeutic implications","volume":"37","author":"Calma","year":"2024","journal-title":"Curr. Opin. Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.neuroscience.2011.02.001","article-title":"Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue","volume":"179","author":"Casula","year":"2011","journal-title":"Neuroscience"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1096\/fj.201700835R","article-title":"Defects in synaptic transmission at the neuromuscular junction precede motor deficits in a TDP\u201043Q331K transgenic mouse model of amyotrophic lateral sclerosis","volume":"32","author":"Chand","year":"2018","journal-title":"FASEB J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12929-016-0290-z","article-title":"Therapeutic effect of berberine on TDP-43-related pathogenesis in FTLD and ALS","volume":"23","author":"Chang","year":"2016","journal-title":"J. Biomed. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.3390\/cells10071789","article-title":"Amyotrophic lateral sclerosis (ALS): stressed by dysfunctional mitochondria-endoplasmic reticulum contacts (MERCs)","volume":"10","author":"Chen","year":"2021","journal-title":"Cells"},{"key":"B34","doi-asserted-by":"publisher","first-page":"925514","DOI":"10.3389\/fphar.2022.925514","article-title":"Research progress on classical traditional chinese medicine formula xiaoyaosan in the treatment of depression","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/s41593-025-01896-4","article-title":"Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis","volume":"28","author":"Cheng","year":"2025","journal-title":"Nat. Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.taap.2012.07.003","article-title":"A new herb\u2013drug interaction of polygonum cuspidatum, a resveratrol\u2010rich nutraceutical, with carbamazepine in rats","volume":"263","author":"Chi","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"767","DOI":"10.2174\/1871527317666180720162029","article-title":"Amyotrophic lateral sclerosis and oxidative stress: a double-blind therapeutic trial after curcumin supplementation","volume":"17","author":"Chico","year":"2018","journal-title":"CNS Neurol. Disord. - Drug Targets"},{"key":"B38","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3389\/fnins.2017.00185","article-title":"Protein quality control by molecular chaperones in neurodegeneration","volume":"11","author":"Ciechanover","year":"2017","journal-title":"Front. Neurosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1126\/science.aaa3650","article-title":"Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways","volume":"347","author":"Cirulli","year":"2015","journal-title":"Science"},{"key":"B40","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.1093\/brain\/awaa309","article-title":"The microglial component of amyotrophic lateral sclerosis","volume":"143","author":"Clarke","year":"2020","journal-title":"Brain"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2312","DOI":"10.1073\/pnas.1815961116","article-title":"Cytotoxic CD8+ T lymphocytes expressing ALS-causing SOD1 mutant selectively trigger death of spinal motoneurons","volume":"116","author":"Coque","year":"2019","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1080\/21678421.2024.2375330","article-title":"Treatment continuity of amyotrophic lateral sclerosis with available riluzole formulations: state of the art and current challenges in a \u2018real-world\u2019 setting","volume":"26","author":"Corcia","year":"2025","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/S1474-4422(14)70222-4","article-title":"Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial","volume":"13","author":"Cudkowicz","year":"2014","journal-title":"LANCET Neurol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"8485","DOI":"10.1007\/s00210-024-03199-0","article-title":"Research progress on pharmacological effects and bioavailability of berberine","volume":"397","author":"Cui","year":"2024","journal-title":"Naunyn. Schmiedeb. Arch. Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"653688","DOI":"10.3389\/fncel.2021.653688","article-title":"The role of mitochondrial dysfunction and ER stress in TDP-43 and C9ORF72 ALS","volume":"15","author":"Dafinca","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1093\/hmg\/dds526","article-title":"RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations","volume":"22","author":"Daigle","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/bs.irn.2024.04.008","article-title":"New developments in pre-clinical models of ALS to guide translation","volume":"176","author":"De Cock","year":"2024","journal-title":"Int. Rev. Neurobiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s00702-010-0520-6","article-title":"Down regulation of trophic factors in neonatal rat spinal cord after administration of cerebrospinal fluid from sporadic amyotrophic lateral sclerosis patients","volume":"118","author":"Deepa","year":"2011","journal-title":"J. Neural Transm."},{"key":"B49","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s11418-019-01367-8","article-title":"Rosmarinic acid in perilla frutescens and perilla herb analyzed by HPLC","volume":"74","author":"Deguchi","year":"2020","journal-title":"J. Nat. Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"B51","doi-asserted-by":"publisher","first-page":"19207","DOI":"10.1021\/acs.jafc.3c05602","article-title":"Bioavailability, health benefits, and delivery systems of allicin: a review","volume":"71","author":"Deng","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"B52","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1146\/annurev-biochem-061516-044908","article-title":"Proteasomal and autophagic degradation systems","volume":"86","author":"Dikic","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"B53","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1111\/cns.13765","article-title":"Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis\u2010associated encephalopathy","volume":"28","author":"Ding","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"B54","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.phymed.2018.03.039","article-title":"G protein-coupled estrogen receptor is involved in the anti-inflammatory effects of genistein in microglia","volume":"43","author":"Du","year":"2018","journal-title":"Phytomedicine"},{"key":"B55","doi-asserted-by":"publisher","first-page":"113259","DOI":"10.1016\/j.expneurol.2020.113259","article-title":"Increased activation ability of monocytes from ALS patients","volume":"328","author":"Du","year":"2020","journal-title":"Exp. Neurol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1038\/sj.ejcn.1601916","article-title":"Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans","volume":"58","author":"DuPont","year":"2004","journal-title":"Eur. J. Clin. Nutr."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic lateral sclerosis","volume":"400","author":"Feldman","year":"2022","journal-title":"Lancet"},{"key":"B58","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1385\/JMN:17:1:89","article-title":"Therapeutic efficacy of EGb761 (Gingko biloba extract) in a transgenic mouse model of amyotrophic lateral sclerosis","volume":"17","author":"Ferrante","year":"2001","journal-title":"J. Mol. Neurosci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e00155","DOI":"10.1128\/MCB.00155-18","article-title":"The C9ORF72 gene, implicated in amyotrophic lateral sclerosis and frontotemporal dementia, encodes a protein that functions in control of endothelin and glutamate signaling","volume":"38","author":"Fomin","year":"2018","journal-title":"Mol. Cell. Biol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"2973","DOI":"10.1007\/s00415-021-10464-2","article-title":"Time-trend evolution and determinants of sex ratio in amyotrophic lateral sclerosis: a dose\u2013response meta-analysis","volume":"268","author":"Fontana","year":"2021","journal-title":"J. Neurol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.neuron.2014.01.013","article-title":"Microglia induce motor neuron death via the classical NF-\u03baB pathway in amyotrophic lateral sclerosis","volume":"81","author":"Frakes","year":"2014","journal-title":"Neuron"},{"key":"B62","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s12974-022-02446-6","article-title":"The role of Th17 cells\/IL-17A in AD, PD, ALS and the strategic therapy targeting on IL-17A","volume":"19","author":"Fu","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"B63","doi-asserted-by":"publisher","first-page":"2476","DOI":"10.3390\/cells12202476","article-title":"Interaction of the C9orf72-amyotrophic lateral sclerosis-related proline\u2013arginine dipeptide repeat protein with the RNA-binding protein NOVA1 causes decreased expression of UNC13A due to enhanced inclusion of cryptic exons, which is reversed by betulin treatment","volume":"12","author":"Fu","year":"2023","journal-title":"Cells"},{"key":"B64","doi-asserted-by":"publisher","first-page":"3420","DOI":"10.1039\/D3FO04760A","article-title":"In vitro study of the blood\u2013brain barrier transport of bioactives from mediterranean foods","volume":"15","author":"Gallardo-Fernandez","year":"2024","journal-title":"Food Funct."},{"key":"B65","doi-asserted-by":"publisher","first-page":"153503","DOI":"10.1016\/j.bbrc.2026.153503","article-title":"Allicin improves motor neuron survival in amyotrophic lateral sclerosis by reducing neuroinflammation and modulating gut microbiota","volume":"809","author":"Gao","year":"2026","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B66","doi-asserted-by":"publisher","first-page":"873224","DOI":"10.3389\/fnagi.2022.873224","article-title":"Mechanism of the curative effect of wen-shen-jian-pi prescription in the treatment of amyotrophic lateral sclerosis","volume":"14","author":"Gong","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"B67","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.brainres.2010.12.014","article-title":"Neuroprotective effects of diallyl trisulfide in SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis","volume":"1374","author":"Guo","year":"2011","journal-title":"Brain Res."},{"key":"B68","doi-asserted-by":"publisher","first-page":"15830","DOI":"10.1074\/jbc.M116.738021","article-title":"Attenuation of PKR-like ER kinase (PERK) signaling selectively controls endoplasmic reticulum stress-induced inflammation without compromising immunological responses","volume":"291","author":"Guthrie","year":"2016","journal-title":"J. Biol. Chem."},{"key":"B69","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1038\/s41467-020-17514-9","article-title":"Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model","volume":"11","author":"Guttenplan","year":"2020","journal-title":"Nat. Commun."},{"key":"B70","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.brainres.2012.09.022","article-title":"Resveratrol upregulated heat shock proteins and extended the survival of G93A-SOD1 mice","volume":"1483","author":"Han","year":"2012","journal-title":"Brain Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/16729","article-title":"Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase","volume":"397","author":"Harding","year":"1999","journal-title":"Nature"},{"key":"B72","doi-asserted-by":"publisher","first-page":"552","DOI":"10.3390\/antiox10040552","article-title":"The interplay of RNA binding proteins, oxidative stress and mitochondrial dysfunction in ALS","volume":"10","author":"Harley","year":"2021","journal-title":"Antioxidants"},{"key":"B73","doi-asserted-by":"publisher","first-page":"953205","DOI":"10.3389\/fphar.2022.953205","article-title":"Best practice in the chemical characterisation of extracts used in pharmacological and toxicological research\u2014the ConPhyMP\u2014Guidelines","volume":"13","author":"Heinrich","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/ana.10805","article-title":"Presence of dendritic cells, MCP\u20101, and activated microglia\/macrophages in amyotrophic lateral sclerosis spinal cord tissue","volume":"55","author":"Henkel","year":"2004","journal-title":"Ann. Neurol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.mcn.2017.07.001","article-title":"TDP-43 in the spectrum of MND-FTLD pathologies","volume":"83","author":"Heyburn","year":"2017","journal-title":"Mol. Cell. Neurosci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/s41580-019-0101-y","article-title":"The proteostasis network and its decline in ageing","volume":"20","author":"Hipp","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1055\/a-1301-8648","article-title":"Rosmarinic acid\u2013human pharmacokinetics and health benefits","volume":"87","author":"Hitl","year":"2021","journal-title":"Planta Med."},{"key":"B78","doi-asserted-by":"publisher","first-page":"8426","DOI":"10.1038\/s41467-024-52539-4","article-title":"Structural basis for the rescue of hyperexcitable cells by the amyotrophic lateral sclerosis drug riluzole","volume":"15","author":"Hollingworth","year":"2024","journal-title":"Nat. Commun."},{"key":"B79","doi-asserted-by":"publisher","first-page":"10958","DOI":"10.3390\/ijms222010958","article-title":"RNA editing: a new therapeutic target in amyotrophic lateral sclerosis and other neurological diseases","volume":"22","author":"Hosaka","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1073\/pnas.032539299","article-title":"Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS)","volume":"99","author":"Howland","year":"2002","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B81","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.3389\/fimmu.2018.03083","article-title":"The C\/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection","volume":"9","author":"Hu","year":"2019","journal-title":"Front. Immunol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s40104-020-00492-9","article-title":"Dietary protocatechuic acid ameliorates inflammation and up-regulates intestinal tight junction proteins by modulating gut microbiota in LPS-challenged piglets","volume":"11","author":"Hu","year":"2020","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1093\/hmg\/ddab101","article-title":"TBN improves motor function and prolongs survival in a TDP-43M337V mouse model of ALS","volume":"30","author":"Huang","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"B84","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41419-020-2642-6","article-title":"Phosphorylation of eukaryotic initiation factor-2\u03b1 (eIF2\u03b1) in autophagy","volume":"11","author":"Humeau","year":"2020","journal-title":"Cell Death Dis."},{"key":"B85","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41419-019-1451-2","article-title":"Targeting the sigma-1 receptor via pridopidine ameliorates central features of ALS pathology in a SOD1G93A model","volume":"10","author":"Ionescu","year":"2019","journal-title":"Cell Death Dis."},{"key":"B86","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.conb.2021.05.003","article-title":"Regulatory roles of mitochondria and metabolism in neurogenesis","volume":"69","author":"Iwata","year":"2021","journal-title":"Curr. Opin. Neurobiol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1002\/med.21528","article-title":"Riluzole and edaravone: a tale of two amyotrophic lateral sclerosis drugs","volume":"39","author":"Jaiswal","year":"2019","journal-title":"Med. Res. Rev."},{"key":"B88","doi-asserted-by":"publisher","first-page":"e25960","DOI":"10.7759\/cureus.25960","article-title":"Ethnical disparities in response to edaravone in patients with amyotrophic lateral sclerosis","volume":"14","author":"Jayasinghe","year":"2022","journal-title":"Cureus"},{"key":"B89","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.bbi.2023.01.013","article-title":"Profiling TREM2 expression in amyotrophic lateral sclerosis","volume":"109","author":"Jeric\u00f3","year":"2023","journal-title":"Brain. Behav. Immun."},{"key":"B90","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.mito.2021.02.008","article-title":"Mitochondrial dysfunction and traffic jams in amyotrophic lateral sclerosis","volume":"58","author":"Jhanji","year":"2021","journal-title":"Mitochondrion"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.tips.2023.08.008","article-title":"ASO drug qalsody (tofersen) targets amyotrophic lateral sclerosis","volume":"44","author":"Jin","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"B92","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1002\/glia.22891","article-title":"NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients: NLRP3 inflammasome expression in ALS","volume":"63","author":"Johann","year":"2015","journal-title":"Glia"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.3389\/fimmu.2018.01289","article-title":"IRE1\u03b1 implications in endoplasmic reticulum stress-mediated development and pathogenesis of autoimmune diseases","volume":"9","author":"Junjappa","year":"2018","journal-title":"Front. Immunol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"367","DOI":"10.3109\/17482968.2012.686511","article-title":"Impaired proteasome function in sporadic amyotrophic lateral sclerosis","volume":"13","author":"Kabashi","year":"2012","journal-title":"Amyotroph. Lateral Scler."},{"key":"B95","doi-asserted-by":"publisher","first-page":"251","DOI":"10.3389\/fnmol.2017.00251","article-title":"Cellular chaperones as therapeutic targets in ALS to restore protein homeostasis and improve cellular function","volume":"10","author":"Kalmar","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"B96","doi-asserted-by":"publisher","first-page":"E11904","DOI":"10.1073\/pnas.1810413115","article-title":"ALS mutations of FUS suppress protein translation and disrupt the regulation of nonsense-mediated decay","volume":"115","author":"Kamelgarn","year":"2018","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1002\/glia.23298","article-title":"Astrocytes expressing ALS\u2010linked mutant FUS induce motor neuron death through release of tumor necrosis factor\u2010alpha","volume":"66","author":"Kia","year":"2018","journal-title":"Glia"},{"key":"B98","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1159\/000090364","article-title":"Celastrol blocks neuronal cell death and extends life in transgenic mouse model of amyotrophic lateral sclerosis","volume":"2","author":"Kiaei","year":"2005","journal-title":"Neurodegener. Dis."},{"key":"B99","doi-asserted-by":"publisher","first-page":"6025","DOI":"10.1073\/pnas.0509227103","article-title":"Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model","volume":"103","author":"Kikuchi","year":"2006","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.3390\/antiox10071011","article-title":"Glutathione in the nervous system as a potential therapeutic target to control the development and progression of amyotrophic lateral sclerosis","volume":"10","author":"Kim","year":"2021","journal-title":"Antioxidants"},{"key":"B101","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/ng.2853","article-title":"Therapeutic modulation of eIF2\u03b1 phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models","volume":"46","author":"Kim","year":"2014","journal-title":"Nat. Genet."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1016\/j.ijbiomac.2018.03.158","article-title":"Gintonin, a ginseng-derived exogenous lysophosphatidic acid receptor ligand, enhances blood-brain barrier permeability and brain delivery","volume":"114","author":"Kim","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.neulet.2005.10.056","article-title":"The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice","volume":"395","author":"Koh","year":"2006","journal-title":"Neurosci. Lett."},{"key":"B104","doi-asserted-by":"publisher","first-page":"5707","DOI":"10.1007\/s00018-021-03872-0","article-title":"DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity","volume":"78","author":"Kok","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"B105","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13024-020-00386-4","article-title":"Impaired NHEJ repair in amyotrophic lateral sclerosis is associated with TDP-43 mutations","volume":"15","author":"Konopka","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"B106","doi-asserted-by":"publisher","first-page":"487","DOI":"10.4142\/jvs.2017.18.4.487","article-title":"KCHO-1, a novel herbal anti-inflammatory compound, attenuates oxidative stress in an animal model of amyotrophic lateral sclerosis","volume":"18","author":"Kook","year":"2017","journal-title":"J. Vet. Sci."},{"key":"B107","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.neulet.2014.02.058","article-title":"7,8-dihydroxyflavone improves motor performance and enhances lower motor neuronal survival in a mouse model of amyotrophic lateral sclerosis","volume":"566","author":"Korkmaz","year":"2014","journal-title":"Neurosci. Lett."},{"key":"B108","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/1020673","article-title":"Bidens pilosa extract administered after symptom onset attenuates glial activation, improves motor performance, and prolongs survival in a mouse model of amyotrophic lateral sclerosis","volume":"2020","author":"Kosuge","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B109","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.3390\/nu12061824","article-title":"Protocatechuic acid extends survival, improves motor function, diminishes gliosis, and sustains neuromuscular junctions in the hSOD1G93A mouse model of amyotrophic lateral sclerosis","volume":"12","author":"Koza","year":"2020","journal-title":"Nutrients"},{"key":"B110","doi-asserted-by":"publisher","first-page":"e74","DOI":"10.1017\/jns.2022.72","article-title":"Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study","volume":"11","author":"Krishnakumar","year":"2022","journal-title":"J. Nutr. Sci."},{"key":"B111","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1523\/JNEUROSCI.4231-07.2008","article-title":"Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular trafficking","volume":"28","author":"Laird","year":"2008","journal-title":"J. Neurosci."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.3390\/cells8121578","article-title":"The impact of kinases in amyotrophic lateral sclerosis at the neuromuscular synapse: insights into BDNF\/TrkB and PKC signaling","volume":"8","author":"Lanuza","year":"2019","journal-title":"Cells"},{"key":"B113","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.ymeth.2004.10.010","article-title":"The ER chaperone and signaling regulator GRP78\/BiP as a monitor of endoplasmic reticulum stress","volume":"35","author":"Lee","year":"2005","journal-title":"Methods"},{"key":"B114","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/1893526","article-title":"Anti-neuroinflammatory effect of jaeumganghwa-tang in an animal model of amyotrophic lateral sclerosis","volume":"2019","author":"Lee","year":"2019","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B115","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12974-015-0310-z","article-title":"Absence of toll-like receptor 4 (TLR4) extends survival in the hSOD1G93A mouse model of amyotrophic lateral sclerosis","volume":"12","author":"Lee","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"B116","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.jgr.2016.12.007","article-title":"Gintonin absorption in intestinal model systems","volume":"42","author":"Lee","year":"2018","journal-title":"J. Ginseng Res."},{"key":"B117","doi-asserted-by":"publisher","first-page":"581942","DOI":"10.3389\/fcell.2020.581942","article-title":"The role of HDAC6 in TDP-43-induced neurotoxicity and UPS impairment","volume":"8","author":"Lee","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B118","doi-asserted-by":"publisher","first-page":"743705","DOI":"10.3389\/fnins.2021.743705","article-title":"Anti-inflammatory effects of a novel herbal extract in the muscle and spinal cord of an amyotrophic lateral sclerosis animal model","volume":"15","author":"Lee","year":"2021","journal-title":"Front. Neurosci."},{"key":"B119","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.7150\/ijbs.16158","article-title":"Changes in the expression of FUS\/TLS in spinal cords of SOD1 G93A transgenic mice and correlation with motor-neuron degeneration","volume":"12","author":"Li","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"B120","doi-asserted-by":"publisher","first-page":"113969","DOI":"10.1016\/j.biopha.2022.113969","article-title":"The clinical application and pharmacological mechanism of bu-zhong-yi-qi decoction for treating cancer-related fatigue: an overview","volume":"156","author":"Li","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B121","doi-asserted-by":"publisher","first-page":"116471","DOI":"10.1016\/j.ejmech.2024.116471","article-title":"Recent advances of honokiol:pharmacological activities, manmade derivatives and structure-activity relationship","volume":"272","author":"Li","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"B122","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s10020-024-00977-7","article-title":"The therapeutic potential of Apigenin in amyotrophic lateral sclerosis through ALDH1A2\/Nrf2\/ARE signaling","volume":"30","author":"Liang","year":"2024","journal-title":"Mol. Med."},{"key":"B123","doi-asserted-by":"publisher","first-page":"988034","DOI":"10.3389\/fneur.2022.988034","article-title":"The efficacy and safety of Chinese herbal medicine as an add-on therapy for amyotrophic lateral sclerosis: an updated systematic review and meta-analysis of randomized controlled trials","volume":"13","author":"Liao","year":"2022","journal-title":"Front. Neurol."},{"key":"B124","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"B125","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/S0896-6273(00)80997-6","article-title":"Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis","volume":"20","author":"Lin","year":"1998","journal-title":"Neuron"},{"key":"B126","doi-asserted-by":"publisher","first-page":"533","DOI":"10.2147\/DDDT.S349678","article-title":"Matrine exerts pharmacological effects through multiple signaling pathways: a comprehensive review","volume":"16","author":"Lin","year":"2022","journal-title":"Drug Des. devel. Ther."},{"key":"B127","doi-asserted-by":"publisher","first-page":"575","DOI":"10.3389\/fnins.2020.00575","article-title":"Peripheral and central nervous system immune response crosstalk in amyotrophic lateral sclerosis","volume":"14","author":"Liu","year":"2020","journal-title":"Front. Neurosci."},{"key":"B128","doi-asserted-by":"publisher","first-page":"1153973","DOI":"10.3389\/fnagi.2023.1153973","article-title":"\u201chuoling shengji granule\u201d for amyotrophic lateral sclerosis: protocol for a multicenter, randomized, double-blind, riluzole parallel controlled clinical trial","volume":"15","author":"Liu","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"B129","doi-asserted-by":"publisher","first-page":"e2461055","DOI":"10.1001\/jamanetworkopen.2024.61055","article-title":"Tetramethylpyrazine nitrone in amyotrophic lateral sclerosis: a randomized clinical trial","volume":"8","author":"Liu","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"B130","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1136\/jnnp-2026-338675","article-title":"Global epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis","author":"Liu","year":"","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B131","doi-asserted-by":"publisher","first-page":"e00953","DOI":"10.1016\/j.neurot.2026.e00953","article-title":"Huoling shengji granule in amyotrophic lateral sclerosis: a multicenter, randomized, double-blind, riluzole-controlled trial","volume":"23","author":"Liu","year":"","journal-title":"Neurotherapeutics"},{"key":"B132","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.neuron.2018.09.044","article-title":"ALS\/FTD-linked mutation in FUS suppresses intra-axonal protein synthesis and drives disease without nuclear loss-of-function of FUS","volume":"100","author":"L\u00f3pez-Erauskin","year":"2018","journal-title":"Neuron"},{"key":"B133","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","article-title":"Poly(GR) in C9ORF72 -related ALS\/FTD compromises mitochondrial function and increases oxidative stress and DNA damage in iPSC-derived motor neurons","volume":"92","author":"Lopez-Gonzalez","year":"2016","journal-title":"Neuron"},{"key":"B134","doi-asserted-by":"publisher","first-page":"12676","DOI":"10.3390\/ijms232012676","article-title":"Discovery of mitophagy inhibitors with therapeutic potential in different familial amyotrophic lateral sclerosis mutations","volume":"23","author":"Maestro","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B135","doi-asserted-by":"publisher","first-page":"e51845","DOI":"10.1371\/journal.pone.0051845","article-title":"Cell-extrinsic effects of tumor ER stress imprint myeloid dendritic cells and impair CD8+ T cell priming","volume":"7","author":"Mahadevan","year":"2012","journal-title":"PLoS ONE"},{"key":"B136","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s12291-015-0502-4","article-title":"Role of endoplasmic reticulum stress and unfolded protein responses in health and diseases","volume":"31","author":"Mahdi","year":"2016","journal-title":"Indian J. Clin. biochem."},{"key":"B137","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s13311-013-0253-y","article-title":"Resveratrol improves motoneuron function and extends survival in SOD1G93A ALS mice","volume":"11","author":"Mancuso","year":"2014","journal-title":"Neurotherapeutics"},{"key":"B138","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1089\/jmf.2009.0243","article-title":"A single-dose resveratrol treatment in a mouse model of amyotrophic lateral sclerosis","volume":"13","author":"Markert","year":"2010","journal-title":"J. Med. Food"},{"key":"B139","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1038\/s41593-025-02075-1","article-title":"C9orf72 hexanucleotide repeat expansions impair microglial response in ALS","volume":"28","author":"Masrori","year":"2025","journal-title":"Nat. Neurosci."},{"key":"B140","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/s41586-019-0924-x","article-title":"Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution","volume":"566","author":"Masuda","year":"2019","journal-title":"Nature"},{"key":"B141","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s00401-018-1933-9","article-title":"Inflammation in ALS\/FTD pathogenesis","volume":"137","author":"McCauley","year":"2019","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"B142","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.bbadis.2013.03.012","article-title":"Rodent models of amyotrophic lateral sclerosis","volume":"1832","author":"McGoldrick","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B143","doi-asserted-by":"publisher","first-page":"3911","DOI":"10.1128\/MCB.00980-14","article-title":"PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation","volume":"34","author":"Meares","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"B144","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1111\/j.1471-4159.2010.07155.x","article-title":"Abnormal exocytotic release of glutamate in a mouse model of amyotrophic lateral sclerosis","volume":"116","author":"Milanese","year":"2011","journal-title":"J. Neurochem."},{"key":"B145","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","article-title":"Trial of antisense oligonucleotide tofersen for SOD1 ALS","volume":"387","author":"Miller","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"B146","doi-asserted-by":"publisher","first-page":"4696","DOI":"10.1073\/pnas.1818415116","article-title":"Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects","volume":"116","author":"Mitra","year":"2019","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B147","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.molcel.2018.01.004","article-title":"Cellular handling of protein aggregates by disaggregation machines","volume":"69","author":"Mogk","year":"2018","journal-title":"Mol. Cell"},{"key":"B148","doi-asserted-by":"publisher","first-page":"179","DOI":"10.2174\/1570159X19666210428120514","article-title":"Plant-derived natural compounds for the treatment of amyotrophic lateral sclerosis: an update","volume":"20","author":"Mohi-ud-din","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"B149","doi-asserted-by":"publisher","first-page":"e65235","DOI":"10.1371\/journal.pone.0065235","article-title":"Inhibition of fast axonal transport by pathogenic SOD1 involves activation of p38 MAP kinase","volume":"8","author":"Morfini","year":"2013","journal-title":"PLoS ONE"},{"key":"B150","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.2174\/138945012803529947","article-title":"Gintonin: a novel ginseng-derived ligand that targets G protein-coupled lysophosphatidic acid receptors","volume":"13","author":"Nah","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"B151","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.jgr.2020.04.002","article-title":"Ginseng gintonin alleviates neurological symptoms in the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis through lysophosphatidic acid 1 receptor","volume":"45","author":"Nam","year":"2021","journal-title":"J. Ginseng Res."},{"key":"B152","doi-asserted-by":"publisher","first-page":"731","DOI":"10.18805\/IJARe.A-5479","article-title":"7, 8- dihydroxyflavone, an effective natural product reduce ralstonia solanacearum populations and control tomato bacterial wilt","volume":"54","author":"Nandhakumar","year":"2020","journal-title":"Indian J. Agric. Res."},{"key":"B153","doi-asserted-by":"publisher","first-page":"121814","DOI":"10.1016\/j.lfs.2023.121814","article-title":"Molecular mechanisms of ischemia and glutamate excitotoxicity","volume":"328","author":"Neves","year":"2023","journal-title":"Life Sci."},{"key":"B154","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1016\/j.neuron.2018.02.027","article-title":"Genome-wide analyses identify KIF5A as a novel ALS gene","volume":"97","author":"Nicolas","year":"2018","journal-title":"Neuron"},{"key":"B155","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/cdd.2014.204","article-title":"Autophagy in the physiology and pathology of the central nervous system","volume":"22","author":"Nikoletopoulou","year":"2015","journal-title":"Cell Death Differ."},{"key":"B156","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1074\/jbc.M109.022012","article-title":"Characterization of alternative isoforms and inclusion body of the TAR DNA-binding protein-43","volume":"285","author":"Nishimoto","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B157","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1146\/annurev-pathol-012513-104649","article-title":"The role of endoplasmic reticulum stress in human pathology","volume":"10","author":"Oakes","year":"2015","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"B158","doi-asserted-by":"publisher","first-page":"e98697","DOI":"10.15252\/embj.201798697","article-title":"NF\u2010\u03baB activation in astrocytes drives a stage\u2010specific beneficial neuroimmunological response in ALS","volume":"37","author":"Ouali Alami","year":"2018","journal-title":"EMBO J."},{"key":"B159","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1073\/pnas.1600251113","article-title":"Acetylcholine receptors from human muscle as pharmacological targets for ALS therapy","volume":"113","author":"Palma","year":"2016","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B160","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/347525","article-title":"Open randomized clinical trial on JWSJZ decoction for the treatment of ALS patients","volume":"2013","author":"Pan","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B161","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1111\/jnc.15255","article-title":"Cellular and physiological functions of C9ORF72 and implications for ALS\/FTD","volume":"157","author":"Pang","year":"2021","journal-title":"J. Neurochem."},{"key":"B162","doi-asserted-by":"publisher","first-page":"8580152","DOI":"10.1155\/2018\/8580152","article-title":"Anti-inflammatory effect of Gamisoyo-San in an animal model of amyotrophic lateral sclerosis","volume":"2018","author":"Park","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B163","doi-asserted-by":"publisher","first-page":"173","DOI":"10.3390\/antiox11010173","article-title":"Combined treatment with herbal medicine and drug ameliorates inflammation and metabolic abnormalities in the liver of an amyotrophic lateral sclerosis mouse model","volume":"11","author":"Park","year":"2022","journal-title":"Antioxidants (Basel)."},{"key":"B164","doi-asserted-by":"publisher","first-page":"104940","DOI":"10.1016\/j.neubiorev.2022.104940","article-title":"Functional MRS studies of GABA and glutamate\/Glx \u2013 a systematic review and meta-analysis","volume":"144","author":"Pasanta","year":"2023","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B165","doi-asserted-by":"publisher","first-page":"614","DOI":"10.3390\/antiox11040614","article-title":"SOD1 in ALS: taking stock in pathogenic mechanisms and the role of glial and muscle cells","volume":"11","author":"Peggion","year":"2022","journal-title":"Antioxidants"},{"key":"B166","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s40478-025-01927-y","article-title":"Kaempferol enhances ER-mitochondria coupling and protects motor neurons from mitochondrial dysfunction and ER stress in C9ORF72-ALS","volume":"13","author":"Pilotto","year":"2025","journal-title":"Acta Neuropathol. Commun."},{"key":"B167","doi-asserted-by":"publisher","first-page":"e1000415","DOI":"10.1371\/journal.pbio.1000415","article-title":"BiP binding to the ER-stress sensor Ire1 tunes the homeostatic behavior of the unfolded protein response","volume":"8","author":"Pincus","year":"2010","journal-title":"PLOS Biol."},{"key":"B168","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fnmol.2019.00025","article-title":"Molecular mechanisms of TDP-43 misfolding and pathology in amyotrophic lateral sclerosis","volume":"12","author":"Prasad","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"B169","doi-asserted-by":"publisher","first-page":"15430","DOI":"10.3390\/ijms242015430","article-title":"The key role of astrocytes in amyotrophic lateral sclerosis and their commitment to glutamate excitotoxicity","volume":"24","author":"Provenzano","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B170","doi-asserted-by":"publisher","first-page":"105274","DOI":"10.1016\/j.phrs.2020.105274","article-title":"HDAC6 as privileged target in drug discovery: a perspective","volume":"163","author":"Pulya","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B171","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1523\/JNEUROSCI.23-07-02627.2003","article-title":"Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons","volume":"23","author":"Rao","year":"2003","journal-title":"J. Neurosci."},{"key":"B172","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1186\/s13287-025-04781-w","article-title":"Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies","volume":"16","author":"Raoufinia","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"B173","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1111\/jnc.13625","article-title":"Physiological functions and pathobiology of TDP \u201043 and FUS\/TLS proteins","volume":"138","author":"Ratti","year":"2016","journal-title":"J. Neurochem."},{"key":"B174","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.3390\/cells9051160","article-title":"Role of endoplasmic reticulum stress sensor IRE1\u03b1 in cellular physiology, calcium, ROS signaling, and metaflammation","volume":"9","author":"Riaz","year":"2020","journal-title":"Cells"},{"key":"B175","doi-asserted-by":"publisher","first-page":"105360","DOI":"10.1016\/j.nbd.2021.105360","article-title":"Lysosome dysfunction as a cause of neurodegenerative diseases: lessons from frontotemporal dementia and amyotrophic lateral sclerosis","volume":"154","author":"Root","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"B176","doi-asserted-by":"publisher","first-page":"123112","DOI":"10.1016\/j.jns.2024.123112","article-title":"High levels of neurofilament light and YKL-40 in cerebrospinal fluid are related to poor outcome in ALS","volume":"463","author":"Ros\u00e9n","year":"2024","journal-title":"J. Neurol. Sci."},{"key":"B177","doi-asserted-by":"publisher","first-page":"533","DOI":"10.2174\/1566524016666160523143937","article-title":"The role of the PERK\/eIF2\u03b1\/ATF4\/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress","volume":"16","author":"Rozpedek","year":"2016","journal-title":"Curr. Mol. Med."},{"key":"B178","doi-asserted-by":"publisher","first-page":"E8294","DOI":"10.1073\/pnas.1704294114","article-title":"Distinct roles for motor neuron autophagy early and late in the SOD1G93A mouse model of ALS","volume":"114","author":"Rudnick","year":"2017","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B179","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1186\/s10020-025-01319-x","article-title":"Syntaphilin loss enhances mitochondrial axonal transport and neuromuscular junction formation in a human stem cell derived neuromuscular assembloid model","volume":"31","author":"Salzinger","year":"2025","journal-title":"Mol. Med."},{"key":"B180","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/nn.4273","article-title":"Modeling ALS with motor neurons derived from human induced pluripotent stem cells","volume":"19","author":"Sances","year":"2016","journal-title":"Nat. Neurosci."},{"key":"B181","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1097\/NEN.0b013e31818b4906","article-title":"Nuclear erythroid 2-related factor 2-antioxidative response element signaling pathway in motor cortex and spinal cord in amyotrophic lateral sclerosis","volume":"67","author":"Sarlette","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B182","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12974-020-01849-7","article-title":"Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment","volume":"17","author":"Schram","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B183","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1242\/jcs.140087","article-title":"Differential roles of the ubiquitin proteasome system (UPS) and autophagy in the clearance of soluble and aggregated TDP-43 species","volume":"127","author":"Scotter","year":"2014","journal-title":"J. Cell Sci."},{"key":"B184","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1248\/bpb.32.382","article-title":"The chinese prescription wen-pi-tang extract delays disease onset in amyotrophic lateral sclerosis model mice while attenuating the activation of glial cells in the spinal cord","volume":"32","author":"Sekiya","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"B185","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.brainres.2010.10.048","article-title":"SK-PC-B70M alleviates neurologic symptoms in G93A-SOD1 amyotrophic lateral sclerosis mice","volume":"1368","author":"Seo","year":"2011","journal-title":"Brain Res."},{"key":"B186","doi-asserted-by":"publisher","first-page":"341","DOI":"10.5607\/en.2015.24.4.341","article-title":"Rosmarinic acid alleviates neurological symptoms in the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis","volume":"24","author":"Seo","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"B187","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1002\/cpdd.1188","article-title":"Safety, pharmacokinetics, and biomarkers of an amorphous solid dispersion of genistein, a radioprotectant, in healthy volunteers","volume":"12","author":"Serebrenik","year":"2023","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"B188","doi-asserted-by":"publisher","first-page":"2400","DOI":"10.3390\/ijms23052400","article-title":"Comprehensive research on past and future therapeutic strategies devoted to treatment of amyotrophic lateral sclerosis","volume":"23","author":"Sever","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B189","doi-asserted-by":"publisher","first-page":"110159","DOI":"10.1016\/j.yebeh.2024.110159","article-title":"Efficacy and tolerability of celastrol and edaravone in the multiple-hit rat model of infantile spasms","volume":"162","author":"Shandra","year":"2025","journal-title":"Epilepsy Behav."},{"key":"B190","doi-asserted-by":"publisher","first-page":"dmm031997","DOI":"10.1242\/dmm.031997","article-title":"Sporadic amyotrophic lateral sclerosis (SALS) \u2013 skeletal muscle response to cerebrospinal fluid from SALS patients in a rat model","volume":"11","author":"Shanmukha","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"B191","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.2174\/1568026611212220010","article-title":"SOD1 aggregation and ALS: role of metallation states and disulfide status","volume":"12","author":"Sheng","year":"2013","journal-title":"Curr. Top. Med. Chem."},{"key":"B192","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1142\/S0192415X00000106","article-title":"Anti-aging effects of the traditional Chinese medicine Bu-Zhong-Yi-Qi-Tang in mice","volume":"28","author":"Shih","year":"2000","journal-title":"Am. J. Chin. Med."},{"key":"B193","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1002\/jnr.22242","article-title":"Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis","volume":"88","author":"Shimojo","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"B194","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1159\/000447559","article-title":"Brain-derived neurotrophic factor facilitates functional recovery from ALS-cerebral spinal fluid-induced neurodegenerative changes in the NSC-34 motor neuron cell line","volume":"17","author":"Shruthi","year":"2017","journal-title":"Neurodegener. Dis."},{"key":"B195","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s00415-006-0301-1","article-title":"Antioxidant capacity and protein oxidation in cerebrospinal fluid of amyotrophic lateral sclerosis","volume":"254","author":"Siciliano","year":"2007","journal-title":"J. Neurol."},{"key":"B196","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/glia.24082","article-title":"The role of endoplasmic reticulum stress in astrocytes","volume":"70","author":"Sims","year":"2022","journal-title":"Glia"},{"key":"B197","doi-asserted-by":"publisher","first-page":"3655","DOI":"10.1016\/j.celrep.2020.02.078","article-title":"Mice carrying ALS mutant TDP-43, but not mutant FUS, display in vivo defects in axonal transport of signaling endosomes","volume":"30","author":"Sleigh","year":"2020","journal-title":"Cell Rep."},{"key":"B198","doi-asserted-by":"publisher","first-page":"132933","DOI":"10.1016\/j.neulet.2017.06.052","article-title":"The role of mitochondria in amyotrophic lateral sclerosis","volume":"710","author":"Smith","year":"2019","journal-title":"Neurosci. Lett."},{"key":"B199","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1007\/s11684-019-0724-6","article-title":"Biological properties and clinical applications of berberine","volume":"14","author":"Song","year":"2020","journal-title":"Front. Med."},{"key":"B200","doi-asserted-by":"publisher","first-page":"946548","DOI":"10.3389\/fphar.2022.946548","article-title":"Herbal medicine for amyotrophic lateral sclerosis: a systematic review and meta-analysis","volume":"13","author":"Song","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B201","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1111\/jnc.14642","article-title":"Endoplasmic reticulum stress is transmissible in vitro between cells of the central nervous system","volume":"148","author":"Sprenkle","year":"2019","journal-title":"J. Neurochem."},{"key":"B202","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1007\/s40262-018-0632-y","article-title":"Clinical pharmacokinetics and pharmacodynamics of drugs in the central nervous system","volume":"57","author":"Srinivas","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"B203","doi-asserted-by":"publisher","first-page":"3854","DOI":"10.3390\/ijms26083854","article-title":"Neuroinflammation and amyotrophic lateral sclerosis: recent advances in anti-inflammatory cytokines as therapeutic strategies","volume":"26","author":"Stacchiotti","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B204","doi-asserted-by":"publisher","first-page":"701886","DOI":"10.3389\/fphar.2021.701886","article-title":"Neuroprotective effects of shenqi fuzheng injection in a transgenic SOD1-G93A mouse model of amyotrophic lateral sclerosis","volume":"12","author":"Sugimoto","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B205","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/5674142","article-title":"Traditional east Asian herbal medicine for amyotrophic lateral sclerosis: a scoping review","volume":"2021","author":"Suh","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B206","doi-asserted-by":"publisher","first-page":"14158","DOI":"10.3390\/ijms241814158","article-title":"Fisetin\u2014In search of better bioavailability\u2014from macro to nano modifications: a review","volume":"24","author":"Szymczak","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B207","doi-asserted-by":"publisher","first-page":"e100999","DOI":"10.15252\/embj.2018100999","article-title":"MITOL prevents ER stress\u2010induced apoptosis by IRE 1\u03b1 ubiquitylation at ER \u2013mitochondria contact sites","volume":"38","author":"Takeda","year":"2019","journal-title":"EMBO J."},{"key":"B208","doi-asserted-by":"publisher","first-page":"e77969","DOI":"10.1371\/journal.pone.0077969","article-title":"Tissue distribution of berberine and its metabolites after oral administration in rats","volume":"8","author":"Tan","year":"2013","journal-title":"PLoS ONE"},{"key":"B209","doi-asserted-by":"publisher","first-page":"4390","DOI":"10.1091\/mbc.e11-06-0510","article-title":"The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress","volume":"22","author":"Teske","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"B210","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1097\/WCO.0000000000000599","article-title":"Neuroinflammatory mechanisms in amyotrophic lateral sclerosis pathogenesis","volume":"31","author":"Thonhoff","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"B211","doi-asserted-by":"publisher","first-page":"130831","DOI":"10.1016\/j.bbagen.2025.130831","article-title":"Baicalein benefits amyotrophic lateral sclerosis via reduction of intraneuronal misfolded protein","volume":"1869","author":"Ting","year":"2025","journal-title":"Biochim. Biophys. Acta GenSubj"},{"key":"B212","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/S1044-7431(03)00022-8","article-title":"Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression","volume":"23","author":"Tortarolo","year":"2003","journal-title":"Mol. Cell. Neurosci."},{"key":"B213","doi-asserted-by":"publisher","first-page":"931968","DOI":"10.3389\/fcell.2022.931968","article-title":"Functional implication of ubiquitinating and deubiquitinating mechanisms in TDP-43 proteinopathies","volume":"10","author":"Tran","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"B214","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/8091","article-title":"SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter","volume":"2","author":"Trotti","year":"1999","journal-title":"Nat. Neurosci."},{"key":"B215","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1101\/gad.335836.119","article-title":"ALS\/FTD-associated protein FUS induces mitochondrial dysfunction by preferentially sequestering respiratory chain complex mRNAs","volume":"34","author":"Tsai","year":"2020","journal-title":"Genes Dev."},{"key":"B216","doi-asserted-by":"publisher","first-page":"13698","DOI":"10.3390\/ijms241813698","article-title":"Anti-inflammatory effects of Miyako Bidens pilosa in a mouse model of amyotrophic lateral sclerosis and lipopolysaccharide-stimulated BV-2 microglia","volume":"24","author":"Tsuruta","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B217","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s00401-025-02913-3","article-title":"Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord","volume":"150","author":"Tuddenham","year":"2025","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"B218","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.jconrel.2020.04.017","article-title":"Astrocyte-derived extracellular vesicles: neuroreparative properties and role in the pathogenesis of neurodegenerative disorders","volume":"323","author":"Upadhya","year":"2020","journal-title":"J. Control Release"},{"key":"B219","doi-asserted-by":"publisher","first-page":"130772","DOI":"10.1016\/j.bbagen.2025.130772","article-title":"The roles of intrinsically disordered proteins in neurodegeneration","volume":"1869","author":"Utami","year":"2025","journal-title":"Biochim. Biophys. Acta BBA - Gen. Subj."},{"key":"B220","doi-asserted-by":"publisher","first-page":"12606","DOI":"10.1038\/s41598-022-16896-8","article-title":"Human iPSC co-culture model to investigate the interaction between microglia and motor neurons","volume":"12","author":"Vahsen","year":"2022","journal-title":"Sci. Rep."},{"key":"B221","doi-asserted-by":"publisher","first-page":"e1610","DOI":"10.1212\/WNL.0000000000007242","article-title":"Revised airlie house consensus guidelines for design and implementation of ALS clinical trials","volume":"92","author":"Van Den Berg","year":"2019","journal-title":"Neurology"},{"key":"B222","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1534\/genetics.117.300262","article-title":"Cell biology of the mitochondrion","volume":"207","author":"Van Der Bliek","year":"2017","journal-title":"Genetics"},{"key":"B223","doi-asserted-by":"publisher","first-page":"e22850","DOI":"10.1371\/journal.pone.0022850","article-title":"Cytoplasmic accumulation and aggregation of TDP-43 upon proteasome inhibition in cultured neurons","volume":"6","author":"Van Eersel","year":"2011","journal-title":"PLoS ONE"},{"key":"B224","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.brainres.2009.01.041","article-title":"Cerebrospinal fluid from sporadic amyotrophic lateral sclerosis patients induces degeneration of a cultured motor neuron cell line","volume":"1263","author":"Vijayalakshmi","year":"2009","journal-title":"Brain Res."},{"key":"B225","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.2174\/1381612829666230529164321","article-title":"Insights into pharmacological potential of apigenin through various pathways on a nanoplatform in multitude of diseases","volume":"29","author":"Waheed","year":"2023","journal-title":"Curr. Pharm. Des."},{"key":"B226","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.neulet.2011.08.047","article-title":"Protective effects of resveratrol through the up-regulation of SIRT1 expression in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of amyotrophic lateral sclerosis","volume":"503","author":"Wang","year":"2011","journal-title":"Neurosci. Lett."},{"key":"B227","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1074\/jbc.M114.617167","article-title":"MFN2 couples glutamate excitotoxicity and mitochondrial dysfunction in motor neurons","volume":"290","author":"Wang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B228","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.neuroscience.2018.03.008","article-title":"Fisetin exerts antioxidant and neuroprotective effects in multiple mutant hSOD1 models of amyotrophic lateral sclerosis by activating ERK","volume":"379","author":"Wang","year":"2018","journal-title":"Neuroscience"},{"key":"B229","doi-asserted-by":"publisher","first-page":"e1007947","DOI":"10.1371\/journal.pgen.1007947","article-title":"TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response","volume":"15","author":"Wang","year":"2019","journal-title":"PLOS Genet."},{"key":"B230","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1093\/hmg\/ddad163","article-title":"Disrupted phase behavior of FUS underlies poly-PR-induced DNA damage in amyotrophic lateral sclerosis","volume":"33","author":"Wang","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"B231","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1111\/bph.16283","article-title":"Kaempferol\u20103\u2010 O \u2010sophoroside (PCS\u20101) contributes to modulation of depressive\u2010like behaviour in C57BL\/6J mice by activating AMPK","volume":"181","author":"Wang","year":"","journal-title":"Br. J. Pharmacol."},{"key":"B232","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1515\/revneuro-2024-0010","article-title":"Current potential pathogenic mechanisms of copper-zinc superoxide dismutase 1 (SOD1) in amyotrophic lateral sclerosis","volume":"35","author":"Wang","year":"","journal-title":"Rev. Neurosci."},{"key":"B233","doi-asserted-by":"publisher","first-page":"108380","DOI":"10.1016\/j.neuropharm.2020.108380","article-title":"Tetramethylpyrazine nitrone improves motor dysfunction and pathological manifestations by activating the PGC-1\u03b1\/Nrf2\/HO-1 pathway in ALS mice","volume":"182","author":"Wen","year":"2021","journal-title":"Neuropharmacology"},{"key":"B234","doi-asserted-by":"publisher","first-page":"107518","DOI":"10.1016\/j.phrs.2024.107518","article-title":"Lycorine protects motor neurons against TDP-43 proteinopathy-induced degeneration in cross-species models with amyotrophic lateral sclerosis","volume":"210","author":"Wen","year":"2024","journal-title":"Pharmacol. Res."},{"key":"B235","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.cell.2018.12.012","article-title":"Environmental control of astrocyte pathogenic activities in CNS inflammation","volume":"176","author":"Wheeler","year":"2019","journal-title":"Cell"},{"key":"B236","doi-asserted-by":"publisher","first-page":"102495","DOI":"10.1016\/j.eclinm.2024.102495","article-title":"Effects of tofersen treatment in patients with SOD1-ALS in a \u201creal-world\u201d setting \u2013 a 12-month multicenter cohort study from the German early access program","volume":"69","author":"Wiesenfarth","year":"2024","journal-title":"eClinicalMedicine"},{"key":"B237","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1136\/jnnp-2022-330504","article-title":"UNC13A in amyotrophic lateral sclerosis: from genetic association to therapeutic target","volume":"94","author":"Willemse","year":"2023","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B238","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1002\/cbdv.200800148","article-title":"Chemical constituents and bioactivities of plants from the genus paeonia","volume":"7","author":"Wu","year":"2010","journal-title":"Chem. Biodivers."},{"key":"B239","doi-asserted-by":"publisher","first-page":"154266","DOI":"10.1016\/j.phymed.2022.154266","article-title":"Lycorine and organ protection: review of its potential effects and molecular mechanisms","volume":"104","author":"Xiao","year":"2022","journal-title":"Phytomedicine"},{"key":"B240","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1023\/B:JOBB.0000041774.12654.e1","article-title":"Mitochondrial degeneration in amyotrophic lateral sclerosis","volume":"36","author":"Xu","year":"2004","journal-title":"J. Bioenerg. Biomembr."},{"key":"B241","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1007\/s11064-006-9166-z","article-title":"Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis","volume":"31","author":"Xu","year":"2006","journal-title":"Neurochem. Res."},{"key":"B242","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.brainres.2013.12.011","article-title":"The molecular link between inefficient GluA2 Q\/R site-RNA editing and TDP-43 pathology in motor neurons of sporadic amyotrophic lateral sclerosis patients","volume":"1584","author":"Yamashita","year":"2014","journal-title":"Brain Res."},{"key":"B243","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1007\/s11655-023-3557-8","article-title":"Combined treatment with bojungikgi-tang (buzhong yiqi decoction) and riluzole attenuates cell death in TDP-43-expressing cells","volume":"30","author":"Yang","year":"2024","journal-title":"Chin. J. Integr. Med."},{"key":"B244","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1159\/000547388","article-title":"Combined herbal medicine (Achyranthes bidentata, Gastrodia elata, and Chaenomeles sinensis) increases anti-inflammatory and anti-oxidative effects in a mouse model of amyotrophic lateral sclerosis","volume":"110","author":"Yang","year":"2025","journal-title":"Pharmacology"},{"key":"B245","doi-asserted-by":"publisher","first-page":"326","DOI":"10.31083\/j.fbl2812326","article-title":"Anti-inflammatory effects of chaenomeles sinensis extract in an ALS animal model","volume":"28","author":"Yang","year":"2023","journal-title":"Front. Biosci. Landmark"},{"key":"B246","doi-asserted-by":"publisher","first-page":"1999953","DOI":"10.1155\/mi\/1999953","article-title":"Herbal medicine extracts improve motor function by anti\u2010inflammatory activity in hSOD1G93A animal model","volume":"2025","author":"Yang","year":"2025","journal-title":"Mediat. Inflamm."},{"key":"B247","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/S0092-8674(01)00611-0","article-title":"XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor","volume":"107","author":"Yoshida","year":"2001","journal-title":"Cell"},{"key":"B248","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/254680","article-title":"Pu-erh tea extract induces the degradation of FET family proteins involved in the pathogenesis of amyotrophic lateral sclerosis","volume":"2014","author":"Yu","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"B249","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1159\/000430769","article-title":"EGb761 ameliorates neuropathic pain by scavenging reactive oxygen species","volume":"95","author":"Yu","year":"2015","journal-title":"Pharmacology"},{"key":"B250","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/j.jgg.2025.05.008","article-title":"Genetic architecture of amyotrophic lateral sclerosis: a comprehensive review","volume":"52","author":"Yuan","year":"2025","journal-title":"J. Genet. Genomics"},{"key":"B251","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/term.2776","article-title":"Reduced sirtuin 1\/adenosine monophosphate\u2010activated protein kinase in amyotrophic lateral sclerosis patient\u2010derived mesenchymal stem cells can be restored by resveratrol","volume":"13","author":"Yun","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"B252","doi-asserted-by":"publisher","first-page":"171","DOI":"10.4103\/2152-7806.169561","article-title":"A comprehensive review of amyotrophic lateral sclerosis","volume":"6","author":"Zarei","year":"2015","journal-title":"Surg. Neurol. Int."},{"key":"B253","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s12904-025-01684-8","article-title":"Actual needs of patients with amyotrophic lateral sclerosis: a qualitative study from wuhan, China","volume":"24","author":"Zeng","year":"2025","journal-title":"BMC Palliat. Care"},{"key":"B254","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.jep.2012.09.005","article-title":"Oral bioavailability and gender-related pharmacokinetics of celastrol following administration of pure celastrol and its related tablets in rats","volume":"144","author":"Zhang","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"B255","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1002\/ptr.4960","article-title":"A review of experimental research on herbal compounds in amyotrophic lateral sclerosis","volume":"28","author":"Zhang","year":"2014","journal-title":"Phytother. Res."},{"key":"B256","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1111\/bph.14102","article-title":"Tetramethylpyrazine nitrone activates the BDNF\/akt\/CREB pathway to promote post\u2010ischaemic neuroregeneration and recovery of neurological functions in rats","volume":"175","author":"Zhang","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"B257","doi-asserted-by":"publisher","first-page":"107777","DOI":"10.1016\/j.neuropharm.2019.107777","article-title":"\u03b3-oryzanol mitigates oxidative stress and prevents mutant SOD1-related neurotoxicity in drosophila and cell models of amyotrophic lateral sclerosis","volume":"160","author":"Zhang","year":"","journal-title":"Neuropharmacology"},{"key":"B258","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.brainresbull.2019.01.019","article-title":"Neuroprotection by urate on the mutant hSOD1-related cellular and drosophila models of amyotrophic lateral sclerosis: implication for GSH synthesis via activating akt\/GSK3\u03b2\/Nrf2\/GCLC pathways","volume":"146","author":"Zhang","year":"","journal-title":"Brain Res. Bull."},{"key":"B259","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neuroscience.2021.04.019","article-title":"Oxymatrine extends survival by attenuating neuroinflammation in a mouse model of amyotrophic lateral sclerosis","volume":"465","author":"Zhang","year":"2021","journal-title":"Neuroscience"},{"key":"B260","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1007\/s11481-019-09866-x","article-title":"Neuroprotective effects of genistein in a SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis","volume":"14","author":"Zhao","year":"2019","journal-title":"J. Neuroimmune Pharmacol."},{"key":"B261","doi-asserted-by":"publisher","first-page":"892518","DOI":"10.3389\/fnagi.2022.892518","article-title":"Towards understanding the relationship between ER stress and unfolded protein response in amyotrophic lateral sclerosis","volume":"14","author":"Zhao","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"B262","doi-asserted-by":"publisher","first-page":"3071","DOI":"10.1002\/fsn3.1168","article-title":"Protocatechuic acid from chicory is bioavailable and undergoes partial glucuronidation and sulfation in healthy humans","volume":"7","author":"Zheng","year":"2019","journal-title":"Food Sci. Nutr."},{"key":"B263","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3389\/fphar.2016.00201","article-title":"Synergistic effects of Chinese herbal medicine: a comprehensive review of methodology and current research","volume":"7","author":"Zhou","year":"2016","journal-title":"Front. Pharmacol."},{"key":"B264","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1038\/s41598-018-19923-9","article-title":"Fingerprint analysis of huolingshengji formula and its neuroprotective effects in SOD1G93A mouse model of amyotrophic lateral sclerosis","volume":"8","author":"Zhou","year":"2018","journal-title":"Sci. Rep."},{"key":"B265","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.apsb.2022.07.019","article-title":"Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis","volume":"13","author":"Zhou","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"B266","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/s41593-020-0619-5","article-title":"Reduced C9ORF72 function exacerbates gain of toxicity from ALS\/FTD-causing repeat expansion in C9orf72","volume":"23","author":"Zhu","year":"2020","journal-title":"Nat. Neurosci."},{"key":"B267","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s13318-024-00877-5","article-title":"Pharmacokinetics, safety profile, and tolerability of tetramethylpyrazine nitrone tablets after single and multiple ascending doses in healthy Chinese volunteers","volume":"49","author":"Zhu","year":"2024","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"B268","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00401-016-1548-y","article-title":"Peripheral monocytes are functionally altered and invade the CNS in ALS patients","volume":"132","author":"Zondler","year":"2016","journal-title":"Acta Neuropathol. (Berl.)"},{"key":"B269","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.nicl.2015.01.009","article-title":"Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [11C]-PBR28","volume":"7","author":"Z\u00fcrcher","year":"2015","journal-title":"NeuroImage Clin."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1918967\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:04:11Z","timestamp":1790244251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1918967\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":269,"alternative-id":["10.3389\/fphar.2026.1918967"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1918967","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"1918967"}}