{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:09:20Z","timestamp":1790071760378,"version":"4.0.1"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Cystatin F (\n                    <jats:italic>CST7<\/jats:italic>\n                    ) has emerged as one of the most consistently upregulated genes identified in transcriptomic and spatial profiling studies of the central nervous system (CNS), particularly within activated microglia and other neuroimmune cell populations. Once regarded primarily as a marker of immune activation, accumulating evidence suggests that the encoded protein, cystatin F, may play a more active role in regulating neuroimmune function through its established ability to modulate lysosomal cysteine proteases. This review synthesizes current knowledge of cystatin F biology and examines its growing relevance across aging, neurodegenerative disease, and CNS inflammation. We first summarize the molecular biology of cystatin F, including its unique intracellular processing, activation, and regulation of cathepsin activity. We then discuss evidence supporting\n                    <jats:italic>CST7<\/jats:italic>\n                    as a conserved marker of activated neuroimmune cells across diverse immune populations and disease-associated cellular states. Next, we review findings implicating\n                    <jats:italic>CST7<\/jats:italic>\n                    across neurodegenerative diseases, highlighting remarkable consistency across distinct pathological contexts. Finally, we examine potential mechanisms linking cystatin F to lysosomal homeostasis, antigen presentation, inflammatory signaling, and cell death pathways. Although direct functional studies within the CNS remain limited, the convergence of biochemical, immunological, and transcriptomic evidence suggests that cystatin F is well positioned to influence neuroimmune responses rather than merely reflect them. Defining the precise role of cystatin F in CNS immunity may therefore provide new insight into the regulation of neuroinflammation and identify novel opportunities for therapeutic intervention across a broad spectrum of neurological diseases.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1959727","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:35:31Z","timestamp":1790069731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cystatin F as a neuroimmune effector in CNS inflammation and neurodegeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Kaitlin","family":"Murray","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Behavior, School of Biological Sciences, University of California","place":["Irvine, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kellie","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California","place":["Irvine, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, School of Biological Sciences, University of California","place":["Irvine, CA, United States"]},{"name":"Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California","place":["Irvine, CA, United States"]},{"name":"Center for Virus Research, University of California","place":["Irvine, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1042\/bss0700179","article-title":"Cystatins","volume":"70","author":"Abrahamson","year":"2003","journal-title":"Biochem. Soc. Symp."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1161\/STROKEAHA.117.020461","article-title":"Diverse inflammatory response after cerebral microbleeds includes coordinated microglial migration and proliferation","volume":"49","author":"Ahn","year":"2018","journal-title":"Stroke"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1242\/jcs.091181","article-title":"Lysosomal cell death at a glance","volume":"126","author":"Aits","year":"2013","journal-title":"J. Cell Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"19195","DOI":"10.1074\/jbc.274.27.19195","article-title":"Inhibition of Mammalian legumain by some cystatins is due to a novel second reactive site","volume":"274","author":"Alvarez-Fernandez","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3390\/biomedicines11010213","article-title":"The biology of lysosomes: from order to disorder","volume":"11","author":"Amaral","year":"2023","journal-title":"Biomedicines"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3894","DOI":"10.1038\/s41467-018-06222-0","article-title":"Single cell molecular alterations reveal target cells and pathways of concussive brain injury","volume":"9","author":"Arneson","year":"2018","journal-title":"Nat. Commun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1622138","DOI":"10.3389\/fcell.2025.1622138","article-title":"Profiling the impact of different tau species on glial cell biology","volume":"13","author":"Arribas Gomez","year":"2025","journal-title":"Front. Cell Dev. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrmicro1343","article-title":"Coronavirus infection of the central nervous system: host-virus stand-off","volume":"4","author":"Bergmann","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nm.2999","article-title":"Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth","volume":"19","author":"Bruchard","year":"2013","journal-title":"Nat. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/nn.3599","article-title":"Identification of a unique TGF-\u03b2-dependent molecular and functional signature in microglia","volume":"17","author":"Butovsky","year":"2014","journal-title":"Nat. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/nri2873","article-title":"Sterile inflammation: sensing and reacting to damage","volume":"10","author":"Chen","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.cell.2020.06.038","article-title":"Spatial transcriptomics and In Situ sequencing to study alzheimer's disease","volume":"182","author":"Chen","year":"2020","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"578133","DOI":"10.1016\/j.jneuroim.2023.578133","article-title":"Ablation of microglia following infection of the central nervous system with a neurotropic murine coronavirus infection leads to increased demyelination and impaired remyelination","volume":"381","author":"Cheng","year":"2023","journal-title":"J. Neuroimmunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/j.1600-0854.2009.00881.x","article-title":"Glycosylation directs targeting and activation of cystatin f from intracellular and extracellular sources","volume":"10","author":"Colbert","year":"2009","journal-title":"Traffic"},{"key":"B15","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e85279","DOI":"10.7554\/eLife.85279","article-title":"Cystatin F (Cst7) drives sex-dependent changes in microglia in an amyloid-driven model of Alzheimer\u2019s disease","volume":"12","author":"Daniels","year":"2023","journal-title":"eLife"},{"key":"B18","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.ejcb.2018.07.002","article-title":"The transcription factor C\/EBP \u03b1 controls the role of cystatin F during the differentiation of monocytes to macrophages","volume":"97","author":"Dautovi\u0107","year":"2018","journal-title":"Eur. J. Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13123019","article-title":"Targeting cathepsins in neurodegeneration: biochemical advances","volume":"13","author":"Di Matteo","year":"2025","journal-title":"Biomedicines"},{"key":"B20","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00018-024-05274-4","article-title":"Cellular depletion of major cathepsin proteases reveals their concerted activities for lysosomal proteolysis","volume":"81","author":"Gallwitz","year":"2024","journal-title":"Cell Mol. Life Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s00401-021-02263-w","article-title":"Distinct amyloid-\u03b2 and tau-associated microglia profiles in alzheimer's disease","volume":"141","author":"Gerrits","year":"2021","journal-title":"Acta Neuropathol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"8441","DOI":"10.1523\/JNEUROSCI.0860-21.2021","article-title":"Spinal cord injury induces permanent reprogramming of microglia into a disease-associated state which contributes to functional recovery","volume":"41","author":"Hakim","year":"2021","journal-title":"J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"16400","DOI":"10.1074\/jbc.273.26.16400","article-title":"Leukocystatin, a new class II cystatin expressed selectively by hematopoietic cells","volume":"273","author":"Halfon","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/ni.1636","article-title":"The NALP3 inflammasome is involved in the innate immune response to amyloid-beta","volume":"9","author":"Halle","year":"2008","journal-title":"Nat. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/sj.emboj.7601979","article-title":"Cystatin F is a cathepsin C-directed protease inhibitor regulated by proteolysis","volume":"27","author":"Hamilton","year":"2008","journal-title":"Embo J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.immuni.2018.11.004","article-title":"Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes","volume":"50","author":"Hammond","year":"2019","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1517\/17425255.4.10.1265","article-title":"Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment","volume":"4","author":"Harry","year":"2008","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s41577-024-01104-7","article-title":"Neuroinflammation in alzheimer disease","volume":"25","author":"Heneka","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1515\/bchm3.1996.377.2.71","article-title":"Cystatins in health and disease","volume":"377","author":"Henskens","year":"1996","journal-title":"Biol. Chem. Hoppe Seyler"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"5440","DOI":"10.4049\/jimmunol.1100790","article-title":"The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-Dependent lysosomal cathepsin B release","volume":"187","author":"Hoegen","year":"2011","journal-title":"J. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e1000648","DOI":"10.1371\/journal.ppat.1000648","article-title":"A protective role for ELR+ chemokines during acute viral encephalomyelitis","volume":"5","author":"Hosking","year":"2009","journal-title":"PLoS Pathog."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.4049\/jimmunol.168.6.2618","article-title":"A role for cathepsin L and cathepsin S in peptide generation for MHC class II presentation","volume":"168","author":"Hsieh","year":"2002","journal-title":"J. Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.0105-2896.2005.00310.x","article-title":"The lysosomal cysteine proteases in MHC class II antigen presentation","volume":"207","author":"Hsing","year":"2005","journal-title":"Immunol. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s40478-021-01239-x","article-title":"Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery","volume":"9","author":"Hunter","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"eaat7554","DOI":"10.1126\/science.aat7554","article-title":"Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation","volume":"363","author":"Jord\u00e3O","year":"2019","journal-title":"Science"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type associated with restricting development of alzheimer\u2019s disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","first-page":"4878","DOI":"10.1182\/blood-2011-10-383083","article-title":"C\/EBP\u03b1 and DEK coordinately regulate myeloid differentiation","volume":"119","author":"Koleva","year":"2012","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1007\/s00262-018-2165-5","article-title":"Cystatin F as a regulator of immune cell cytotoxicity","volume":"67","author":"Kos","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"B40","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e202005072","DOI":"10.1083\/jcb.202005072","article-title":"Phagosome resolution regenerates lysosomes and maintains the degradative capacity in phagocytes","volume":"220","author":"Lancaster","year":"2021","journal-title":"J. Cell Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1615\/critrevimmunol.v30.i2.20","article-title":"The pathogenesis of murine coronavirus infection of the central nervous system","volume":"30","author":"Lane","year":"2010","journal-title":"Crit. Rev. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1111\/j.1742-4658.2005.04594.x","article-title":"Inhibitory properties of cystatin F and its localization in U937 promonocyte cells","volume":"272","author":"Langerholc","year":"2005","journal-title":"Febs J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s00401-016-1631-4","article-title":"Multiple sclerosis: experimental models and reality","volume":"133","author":"Lassmann","year":"2017","journal-title":"Acta Neuropathol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"eabm7134","DOI":"10.1126\/scisignal.abm7134","article-title":"Disruptions in endocytic traffic contribute to the activation of the NLRP3 inflammasome","volume":"16","author":"Lee","year":"2023","journal-title":"Sci. Signal."},{"key":"B46","doi-asserted-by":"publisher","first-page":"8783","DOI":"10.1038\/s41598-023-35975-y","article-title":"Necrosulfonamide exerts neuroprotective effect by inhibiting necroptosis, neuroinflammation, and \u03b1-synuclein oligomerization in a subacute MPTP mouse model of parkinson's disease","volume":"13","author":"Leem","year":"2023","journal-title":"Sci. Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"eabo2810","DOI":"10.1126\/sciadv.abo2810","article-title":"Mechanisms of antigen-induced reversal of CNS inflammation in experimental demyelinating disease","volume":"9","author":"Li","year":"","journal-title":"Sci. Adv."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1038\/s43587-023-00479-x","article-title":"Transcriptional and epigenetic decoding of the microglial aging process","volume":"3","author":"Li","year":"","journal-title":"Nat. Aging"},{"key":"B49","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s12974-024-03119-2","article-title":"Monocytes release cystatin F dimer to associate with A\u03b2 and aggravate amyloid pathology and cognitive deficits in Alzheimer\u2019s disease","volume":"21","author":"Li","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"B50","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3389\/fnmol.2016.00152","article-title":"Disinhibition of cathepsin C caused by cystatin F deficiency aggravates the demyelination in a cuprizone model","volume":"9","author":"Liang","year":"2016","journal-title":"Front. Mol. Neurosci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12974-019-1398-3","article-title":"Cathepsin C promotes microglia M1 polarization and aggravates neuroinflammation via activation of Ca(2+)-dependent PKC\/p38MAPK\/NF-\u03baB pathway","volume":"16","author":"Liu","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"B52","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/s41582-019-0184-2","article-title":"The pro-remyelination properties of microglia in the central nervous system","volume":"15","author":"Lloyd","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s11064-006-9183-y","article-title":"Induced expression of cathepsins and cystatin C in a murine model of demyelination","volume":"32","author":"Ma","year":"2007","journal-title":"Neurochem. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1002\/jnr.22567","article-title":"Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination","volume":"89","author":"Ma","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"45","DOI":"10.7150\/jca.5044","article-title":"Cystatins in immune system","volume":"4","author":"Magister","year":"2013","journal-title":"J. Cancer"},{"key":"B56","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.ejcb.2012.01.001","article-title":"Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells","volume":"91","author":"Magister","year":"2012","journal-title":"Eur. J. Cell Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13041-019-0504-x","article-title":"Autophagic and endo-lysosomal dysfunction in neurodegenerative disease","volume":"12","author":"Malik","year":"2019","journal-title":"Mol. Brain"},{"key":"B58","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1002\/glia.23844","article-title":"Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system","volume":"68","author":"Mangale","year":"2020","journal-title":"Glia"},{"key":"B59","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":"B60","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.celrep.2020.01.010","article-title":"Microglia heterogeneity in the single-cell era","volume":"30","author":"Masuda","year":"2020","journal-title":"Cell Rep."},{"key":"B61","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1038\/s41586-019-1329-6","article-title":"Author correction: single-Cell transcriptomic analysis of alzheimer's disease","volume":"571","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"B62","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1006\/geno.2000.6237","article-title":"Genomic construct and mapping of the gene for CMAP (Leukocystatin\/Cystatin F, CST7) and identification of a proximal novel gene, BSCv (C20orf3)","volume":"67","author":"Morita","year":"2000","journal-title":"Genomics"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e70357","DOI":"10.1111\/acel.70357","article-title":"Deciphering the transcriptomic signatures of aging across organs in mice","volume":"25","author":"Morsy","year":"2026","journal-title":"Aging Cell"},{"key":"B64","doi-asserted-by":"publisher","first-page":"5502","DOI":"10.1046\/j.1432-1033.2002.03252.x","article-title":"Regulated expression and intracellular localization of cystatin F in human U937 cells","volume":"269","author":"Nathanson","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"B65","doi-asserted-by":"publisher","first-page":"24797","DOI":"10.1074\/jbc.273.38.24797","article-title":"Cystatin F is a glycosylated human low molecular weight cysteine proteinase inhibitor","volume":"273","author":"Ni","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1023\/a:1007675508413","article-title":"The endosomal-lysosomal system of neurons in alzheimer's disease pathogenesis: a review","volume":"25","author":"Nixon","year":"2000","journal-title":"Neurochem. Res."},{"key":"B67","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1353\/hpu.0.0257","article-title":"Cystatin superfamily","volume":"21","author":"Ochieng","year":"2010","journal-title":"J. Health Care Poor Underserved"},{"key":"B68","doi-asserted-by":"publisher","first-page":"E8788","DOI":"10.1073\/pnas.1714175114","article-title":"RIPK1 mediates a disease-associated microglial response in alzheimer's disease","volume":"114","author":"Ofengeim","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/s43587-022-00310-z","article-title":"Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying alzheimer's disease pathology","volume":"2","author":"Pereira","year":"2022","journal-title":"Nat. Aging"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.3389\/fimmu.2017.01459","article-title":"Cystatin F affects natural killer cell cytotoxicity","volume":"8","author":"Peri\u0161I\u0107 Nanut","year":"2017","journal-title":"Front. Immunol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.3390\/cells11152383","article-title":"Profiling microglia through single-cell RNA sequencing over the course of development, aging, and disease","volume":"11","author":"Pettas","year":"2022","journal-title":"Cells"},{"key":"B72","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1128\/JVI.06797-11","article-title":"CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis","volume":"86","author":"Phares","year":"2012","journal-title":"J. Virol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.3390\/biom11121796","article-title":"New insights into the role of cysteine cathepsins in neuroinflammation","volume":"11","author":"Pi\u0161LAR","year":"2021","journal-title":"Biomolecules"},{"key":"B74","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1002\/glia.24318","article-title":"Alzheimer's disease-associated R47H TREM2 increases, but wild-type TREM2 decreases, microglial phagocytosis of synaptosomes and neuronal loss","volume":"71","author":"Popescu","year":"2023","journal-title":"Glia"},{"key":"B75","doi-asserted-by":"publisher","first-page":"57","DOI":"10.2478\/raon-2019-0007","article-title":"Increased cystatin F levels correlate with decreased cytotoxicity of cytotoxic T cells","volume":"53","author":"Prunk","year":"2019","journal-title":"Radiol. Oncol."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123660","article-title":"Extracellular cystatin F is internalised by cytotoxic T lymphocytes and decreases their cytotoxicity","volume":"12","author":"Prunk","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B77","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s12974-023-02866-y","article-title":"Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration","volume":"20","author":"Quick","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"B78","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1126\/science.aag2590","article-title":"How neuroinflammation contributes to neurodegeneration","volume":"353","author":"Ransohoff","year":"2016","journal-title":"Science"},{"key":"B79","doi-asserted-by":"publisher","first-page":"eabn5648","DOI":"10.1126\/science.abn5648","article-title":"The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection","volume":"378","author":"Richards","year":"2022","journal-title":"Science"},{"key":"B80","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/s1074-7613(00)80249-6","article-title":"Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading","volume":"4","author":"Riese","year":"1996","journal-title":"Immunity"},{"key":"B81","doi-asserted-by":"publisher","first-page":"3085","DOI":"10.4049\/jimmunol.1002051","article-title":"Recognition of cytoplasmic RNA results in cathepsin-dependent inflammasome activation and apoptosis in human macrophages","volume":"186","author":"Rintahaka","year":"2011","journal-title":"J. Immunol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/j.neuron.2021.01.027","article-title":"White matter aging drives microglial diversity","volume":"109","author":"Safaiyan","year":"2021","journal-title":"Neuron"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.celrep.2019.03.099","article-title":"The major risk factors for alzheimer's disease: age, sex, and genes modulate the microglia response to A\u03b2 plaques","volume":"27","author":"Sala Frigerio","year":"2019","journal-title":"Cell Rep."},{"key":"B84","doi-asserted-by":"publisher","first-page":"13800","DOI":"10.1074\/jbc.274.20.13800","article-title":"Molecular cloning and structural and functional characterization of human cathepsin F, a new cysteine proteinase of the papain family with a long propeptide domain","volume":"274","author":"Santamar\u00edA","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B85","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/1742-2094-9-104","article-title":"IFN-\u03b3 protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils","volume":"9","author":"Savarin","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169089","article-title":"The key role of lysosomal protease cathepsins in viral infections","volume":"23","author":"Scarcella","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"3754","DOI":"10.1038\/s41467-023-39060-w","article-title":"Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of parkinson disease","volume":"14","author":"Schonhoff","year":"2023","journal-title":"Nat. Commun."},{"key":"B88","doi-asserted-by":"publisher","first-page":"16570","DOI":"10.1074\/jbc.M601033200","article-title":"Structural basis of reduction-dependent activation of human cystatin F","volume":"281","author":"Sch\u00fcTTELKOPF","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B89","doi-asserted-by":"publisher","first-page":"eadx0043","DOI":"10.1126\/science.adx0043","article-title":"Neuroinflammation across neurological diseases","volume":"388","author":"Shi","year":"2025","journal-title":"Science"},{"key":"B90","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1038\/nm.2749","article-title":"Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain","volume":"18","author":"Shichita","year":"2012","journal-title":"Nat. Med."},{"key":"B91","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1002\/glia.23134","article-title":"The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1-overexpressing mouse, a chronic demyelinating disease model","volume":"65","author":"Shimizu","year":"2017","journal-title":"Glia"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40478-020-01099-x","article-title":"Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of alzheimer's disease","volume":"9","author":"Sobue","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"B93","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s44400-026-00086-8","article-title":"\u201cMicro-managing\u201d immune activation and protein turnover: microglial lysosomes in the context of health and disease","volume":"2","author":"Somodji","year":"2026","journal-title":"Npj Dement."},{"key":"B94","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41593-018-0083-7","article-title":"Microglia-mediated recovery from ALS-Relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy","volume":"21","author":"Spiller","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1038\/s41556-026-02007-6","article-title":"Lysosomes and lysosomal dysfunction in ageing biology","volume":"28","author":"Steinhauser","year":"2026","journal-title":"Nat. Cell Biol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.arr.2016.04.010","article-title":"Lysosomal cathepsins and their regulation in aging and neurodegeneration","volume":"32","author":"Stoka","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"B97","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13024-020-00397-1","article-title":"The role of TDP-43 mislocalization in amyotrophic lateral sclerosis","volume":"15","author":"Suk","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1621789","DOI":"10.3389\/fimmu.2025.1621789","article-title":"Evolving insights on the role of microglia in neuroinflammation, plasticity, and regeneration of the injured spinal cord","volume":"16","author":"Swarts","year":"2025","journal-title":"Front. Immunol."},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01295-20","article-title":"Single-cell RNA sequencing reveals the diversity of the immunological landscape following central nervous system infection by a murine coronavirus","volume":"94","author":"Syage","year":"2020","journal-title":"J. Virol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1291255","DOI":"10.3389\/fncel.2023.1291255","article-title":"Microglia influence immune responses and restrict neurologic disease in response to central nervous system infection by a neurotropic murine coronavirus","volume":"17","author":"Syage","year":"2023","journal-title":"Front. Cell Neurosci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s12974-024-03153-0","article-title":"Cystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system","volume":"21","author":"Syage","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"B102","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jneuroim.2007.10.030","article-title":"Role of IFN-Gamma responsiveness in CD8 T-cell-mediated viral clearance and demyelination in coronavirus-infected mice","volume":"194","author":"Templeton","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"108189","DOI":"10.1016\/j.celrep.2020.108189","article-title":"Single-nucleus RNA-seq is not suitable for detection of microglial activation genes in humans","volume":"32","author":"Thrupp","year":"2020","journal-title":"Cell Rep."},{"key":"B104","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/0014-5793(91)80804-c","article-title":"The cystatins: protein inhibitors of cysteine proteinases","volume":"285","author":"Turk","year":"1991","journal-title":"FEBS Lett."},{"key":"B105","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/s1074-7613(00)80176-4","article-title":"Proteolysis in MHC class II antigen presentation: who's in charge?","volume":"12","author":"Villadangos","year":"2000","journal-title":"Immunity"},{"key":"B106","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12974-025-03526-z","article-title":"Cystatin F-a key player in central nervous system disease","volume":"22","author":"Wang","year":"2025","journal-title":"J. Neuroinflammation"},{"key":"B107","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1172\/JCI97229","article-title":"Microglia are required for protection against lethal coronavirus encephalitis in mice","volume":"128","author":"Wheeler","year":"2018","journal-title":"J. Clin. Invest."},{"key":"B108","doi-asserted-by":"publisher","first-page":"1700692","DOI":"10.3389\/fncel.2025.1700692","article-title":"Microglia-orchestrated neuroinflammation and synaptic remodeling: roles of pro-inflammatory cytokines and receptors in neurodegeneration","volume":"19","author":"Yang","year":"2025","journal-title":"Front. Cell Neurosci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"7400","DOI":"10.21037\/tcr-2025-1943","article-title":"CST7(+) macrophages\/monocytes in melanoma: single-cell insights into immunotherapy response","volume":"14","author":"Yao","year":"2025","journal-title":"Transl. Cancer Res."},{"key":"B110","doi-asserted-by":"publisher","first-page":"e00018","DOI":"10.1097\/IN9.0000000000000018","article-title":"The role of ApoE-mediated microglial lipid metabolism in brain aging and disease","volume":"5","author":"Yen","year":"2023","journal-title":"Immunometabolism"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1038\/nm.3700","article-title":"Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in alzheimer's disease","volume":"20","author":"Zhang","year":"2014","journal-title":"Nat. Med."},{"key":"B112","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.1038\/s41467-022-33226-8","article-title":"Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"B113","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s40364-024-00711-9","article-title":"The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases","volume":"12","author":"Zhao","year":"2024","journal-title":"Biomark. Res."},{"key":"B114","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1177\/0271678X211026770","article-title":"Single-cell RNA-Seq reveals the transcriptional landscape in ischemic stroke","volume":"42","author":"Zheng","year":"2022","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"B115","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41591-019-0695-9","article-title":"Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in alzheimer's disease","volume":"26","author":"Zhou","year":"2020","journal-title":"Nat. Med."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1959727\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:35:32Z","timestamp":1790069732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1959727\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":115,"alternative-id":["10.3389\/fcell.2026.1959727"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1959727","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1959727"}}