{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:07:44Z","timestamp":1791925664054,"version":"4.3.4"},"reference-count":148,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson\u2019s disease, Alzheimer\u2019s disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington\u2019s disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as \u03b1-synuclein and amyloid-\u03b2 clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.<\/jats:p>","DOI":"10.3390\/ijms26167886","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T16:09:55Z","timestamp":1755274195000},"page":"7886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cathepsins in Neurological Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0973-053X","authenticated-orcid":false,"given":"Dominik","family":"Lewandowski","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0191-0186","authenticated-orcid":false,"given":"Mateusz","family":"Konieczny","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-5956","authenticated-orcid":false,"given":"Agata","family":"R\u00f3\u017cycka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Chrzanowski","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Owecki","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8171-9208","authenticated-orcid":false,"given":"Jan","family":"Kalinowski","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miko\u0142aj","family":"Stepura","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9046-6802","authenticated-orcid":false,"given":"Pawe\u0142","family":"Jagodzi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-0403","authenticated-orcid":false,"given":"Jolanta","family":"Dorszewska","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.brainres.2015.08.031","article-title":"How microglia kill neurons","volume":"1628 Pt B","author":"Brown","year":"2015","journal-title":"Brain Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.neuroscience.2007.02.055","article-title":"Neuroprotective role of the innate immune system by microglia","volume":"147","author":"Glezer","year":"2007","journal-title":"Neuroscience"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbapap.2011.10.002","article-title":"Cysteine cathepsins: From structure, function and regulation to new frontiers","volume":"1824","author":"Turk","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/nrd2092","article-title":"Targeting proteases: Successes, failures and future prospects","volume":"5","author":"Turk","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1756-6606-1-17","article-title":"Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity","volume":"1","author":"Qiao","year":"2008","journal-title":"Mol. Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1750-1326-6-52","article-title":"Upregulation of cathepsin D in the caudate nucleus of primates with experimental parkinsonism","volume":"6","author":"Yelamanchili","year":"2011","journal-title":"Mol. Neurodegener."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12974-015-0268-x","article-title":"The induction of neuronal death by up-regulated microglial cathepsin H in LPS-induced neuroinflammation","volume":"12","author":"Fan","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7883","DOI":"10.1073\/pnas.112632299","article-title":"Neuronal loss and brain atrophy in mice lacking cathepsins B and L","volume":"99","author":"Felbor","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cermak, S., Kosicek, M., Mladenovic-Djordjevic, A., Smiljanic, K., Kanazir, S., and Hecimovic, S. (2016). Loss of Cathepsin B and L leads to lysosomal dysfunction, NPC-like cholesterol sequestration and accumulation of the key Alzheimer\u2019s proteins. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167428"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1046\/j.1471-4159.1996.67051846.x","article-title":"Cytosolic proteolysis of tau by cathepsin D in hippocampus following suppression of cathepsins B and L","volume":"67","author":"Bednarski","year":"1996","journal-title":"J. Neurochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.neuropharm.2016.11.019","article-title":"Inhibition of cathepsin X reduces the strength of microglial-mediated neuroinflammation","volume":"114","author":"Zidar","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neurobiolaging.2019.02.010","article-title":"Old age increases microglial senescence, exacerbates secondary neuroinflammation, and worsens neurological outcomes after acute traumatic brain injury in mice","volume":"77","author":"Ritzel","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1742-2094-9-96","article-title":"Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation","volume":"9","author":"Fan","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liang, J., Li, N., Zhang, Y., Hou, C., Yang, X., Shimizu, T., Wang, X., Ikenaka, K., Fan, K., and Ma, J. (2016). Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model. Front. Mol. Neurosci., 9.","DOI":"10.3389\/fnmol.2016.00152"},{"key":"ref_15","doi-asserted-by":"crossref","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":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.brainres.2008.07.067","article-title":"Upregulation of cathepsin S in the aging and pathological nervous system of mice","volume":"1232","author":"Wendt","year":"2008","journal-title":"Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dauth, S., S\u00eerbulescu, R.F., Jordans, S., Rehders, M., Avena, L., Oswald, J., Lerchl, A., Saftig, P., and Brix, K. (2011). Cathepsin K deficiency in mice induces structural and metabolic changes in the central nervous system that are associated with learning and memory deficits. BMC Neurosci., 12.","DOI":"10.1186\/1471-2202-12-74"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e464","DOI":"10.1016\/S2666-7568(24)00094-1","article-title":"Temporal trends in the prevalence of Parkinson\u2019s disease from 1980 to 2023: A systematic review and meta-analysis","volume":"5","author":"Zhu","year":"2024","journal-title":"Lancet Healthy Longev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Luo, Y., Qiao, L., Li, M., Wen, X., Zhang, W., and Li, X. (2024). Global, regional, national epidemiology and trends of Parkinson\u2019s disease from 1990 to 2021: Findings from the Global Burden of Disease Study 2021. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1498756"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e080952","DOI":"10.1136\/bmj-2024-080952","article-title":"Projections for prevalence of Parkinson\u2019s disease and its driving factors in 195 countries and territories to 2050: Modelling study of Global Burden of Disease Study 2021","volume":"388","author":"Su","year":"2025","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and treatment of Parkinson disease: A review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0140-6736(23)01478-2","article-title":"The pathogenesis of Parkinson\u2019s disease","volume":"403","author":"Morris","year":"2024","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2217\/epi-2023-0416","article-title":"Epigenetics and the neurodegenerative process","volume":"16","author":"Owecki","year":"2024","journal-title":"Epigenomics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1093\/brain\/awad388","article-title":"Nigrostriatal tau pathology in parkinsonism and Parkinson\u2019s disease","volume":"147","author":"Chu","year":"2024","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1750-1326-9-43","article-title":"Alpha-synuclein and tau: Teammates in neurodegeneration?","volume":"9","author":"Moussaud","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yusufujiang, A., Zeng, S., and Li, H. (2024). Cathepsins and Parkinson\u2019s disease: Insights from Mendelian randomization analyses. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1380483"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9322","DOI":"10.1073\/pnas.1500937112","article-title":"Cysteine cathepsins are essential in lysosomal degradation of \u03b1-synuclein","volume":"112","author":"McGlinchey","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.parkreldis.2019.11.015","article-title":"Autophagy lysosomal pathway dysfunction in Parkinson\u2019s disease; evidence from human genetics","volume":"73","author":"Senkevich","year":"2020","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1080\/15548627.2022.2045534","article-title":"Recombinant pro-CTSD (cathepsin D) enhances SNCA\/\u03b1-synuclein degradation in \u03b1-synucleinopathy models","volume":"18","author":"Drobny","year":"2022","journal-title":"Autophagy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/cts.12920","article-title":"Identification of BAG2 and cathepsin D as plasma biomarkers for Parkinson\u2019s disease","volume":"14","author":"Kang","year":"2021","journal-title":"Clin. Transl. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/mds.27136","article-title":"Cerebrospinal fluid \u03b2-glucocerebrosidase activity is reduced in Parkinson\u2019s disease patients","volume":"32","author":"Parnetti","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/mds.25495","article-title":"Changes in endolysosomal enzyme activities in cerebrospinal fluid of patients with Parkinson\u2019s disease","volume":"28","author":"Persichetti","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neulet.2010.11.068","article-title":"Parkinson\u2019s disease involves autophagy and abnormal distribution of cathepsin L","volume":"489","author":"Li","year":"2011","journal-title":"Neurosci. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e70207","DOI":"10.1002\/brb3.70207","article-title":"Genetic insights into the role of cathepsins in Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis: Evidence from Mendelian randomization study","volume":"15","author":"Jiang","year":"2025","journal-title":"Brain Behav."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lu, C., Cai, X., Zhi, S., Wen, X., Shen, J., Ercoli, T., Simula, E.R., Masala, C., Sechi, L.A., and Solla, P. (2024). Exploring the association between cathepsin B and Parkinson\u2019s disease. Brain Sci., 14.","DOI":"10.3390\/brainsci14050482"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41420-025-02343-w","article-title":"Cathepsin B prevents cell death by fragmentation and destruction of pathological amyloid fibrils","volume":"11","author":"Sulatsky","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13024-024-00779-9","article-title":"The Parkinson\u2019s disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons","volume":"19","author":"He","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Aufschnaiter, A., Habernig, L., Kohler, V., Diessl, J., Carmona-Gutierrez, D., Eisenberg, T., Keller, W., and B\u00fcttner, S. (2017). The coordinated action of calcineurin and cathepsin D protects against \u03b1-synuclein toxicity. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00207"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40035-023-00363-z","article-title":"Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models","volume":"12","author":"Drobny","year":"2023","journal-title":"Transl. Neurodegener."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0022-510X(95)00035-Z","article-title":"Comparison of cathepsin protease activities in brain tissue from normal cases and cases with Alzheimer\u2019s disease, Lewy body dementia, Parkinson\u2019s disease and Huntington\u2019s disease","volume":"131","author":"Mantle","year":"1995","journal-title":"J. Neurol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.nbd.2017.11.006","article-title":"The lysosomal enzyme alpha-galactosidase A is deficient in Parkinson\u2019s disease brain in association with the pathologic accumulation of alpha-synuclein","volume":"110","author":"Nelson","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1007\/s12035-018-1090-0","article-title":"Characterization of brain lysosomal activities in GBA-related and sporadic Parkinson\u2019s disease and dementia with Lewy bodies","volume":"56","author":"Moors","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wu, H.C., Chang, K.H., Chiang, M.C., and Chen, C.M. (2021). Alterations of plasma galectin-3 and C3 levels in patients with Parkinson\u2019s disease. Brain Sci., 11.","DOI":"10.3390\/brainsci11111515"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00702-003-0832-x","article-title":"Modulation of disease risk according to a cathepsin D \/ apolipoprotein E genotype in Parkinson\u2019s disease","volume":"110","author":"Schulte","year":"2003","journal-title":"J. Neural Transm."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bezrukova, A.I., Basharova, K.S., Emelyanov, A.K., Rybakov, A.V., Miliukhina, I.V., Pchelina, S.N., and Usenko, T.S. (2025). Autophagy process in Parkinson\u2019s disease depends on mutations in the GBA1 and LRRK2 genes. Biochem. Genet.","DOI":"10.1007\/s10528-025-11125-z"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1007\/s11596-018-1977-z","article-title":"LRRK2 G2019S mutation inhibits degradation of \u03b1-synuclein in an in vitro model of Parkinson\u2019s disease","volume":"38","author":"Hu","year":"2018","journal-title":"Curr. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5506","DOI":"10.1039\/C8SC01109E","article-title":"C-terminal truncation of \u03b1-synuclein promotes amyloid fibril amplification at physiological pH","volume":"9","author":"Knowles","year":"2018","journal-title":"Chem. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22670","DOI":"10.1074\/jbc.M501508200","article-title":"A precipitating role for truncated alpha-synuclein and the proteasome in alpha-synuclein aggregation: Implications for pathogenesis of Parkinson disease","volume":"280","author":"Liu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9973","DOI":"10.1074\/jbc.RA119.008930","article-title":"C-terminal \u03b1-synuclein truncations are linked to cysteine cathepsin activity in Parkinson\u2019s disease","volume":"294","author":"McGlinchey","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.nbd.2014.10.011","article-title":"Lysosomal enzyme cathepsin B enhances the aggregate forming activity of exogenous \u03b1-synuclein fibrils","volume":"73","author":"Tsujimura","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ferree, A.W. (2019). Cathepsin oxidation alters alpha-synuclein processing. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00530"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4103\/1673-5374.264444","article-title":"Microglial cathepsin B as a key driver of inflammatory brain diseases and brain aging","volume":"15","author":"Nakanishi","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1742-2094-5-8","article-title":"Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson\u2019s disease","volume":"5","author":"Koprich","year":"2008","journal-title":"J. Neuroinflamm."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13024-016-0094-3","article-title":"MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson\u2019s disease","volume":"11","author":"Zhou","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pi\u0161lar, A., Tratnjek, L., Glavan, G., \u017divin, M., and Kos, J. (2018). Upregulation of cysteine protease cathepsin X in the 6-hydroxydopamine model of Parkinson\u2019s disease. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00412"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropharm.2013.07.040","article-title":"Cathepsin X promotes 6-hydroxydopamine-induced apoptosis of PC12 and SH-SY5Y cells","volume":"82","author":"Zidar","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/1440-1681.13052","article-title":"Knockdown of cathepsin D protects dopaminergic neurons against neuroinflammation-mediated neurotoxicity through inhibition of NF-\u03baB signalling pathway in Parkinson\u2019s disease model","volume":"46","author":"Gan","year":"2019","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e169594","DOI":"10.1172\/jci.insight.169594","article-title":"Inhibition of cysteine protease cathepsin L increases the level and activity of lysosomal glucocerebrosidase","volume":"9","author":"Kim","year":"2024","journal-title":"JCI Insight"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lin, L., Wu, Z., Luo, H., and Huang, Y. (2024). Cathepsin-mediated regulation of alpha-synuclein in Parkinson\u2019s disease: A Mendelian randomization study. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1394807"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sun, H., Tang, Q., Yan, X., Xie, W., Xu, Y., and Zhang, W. (2024). Cathepsins and neurological diseases: A Mendelian randomization study. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1454369"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40035-024-00432-x","article-title":"Updates in Alzheimer\u2019s disease: From basic research to diagnosis and therapies","volume":"13","author":"Liu","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/procel\/pwae026","article-title":"Alzheimer\u2019s disease: Insights into pathology, molecular mechanisms and therapy","volume":"16","author":"Zheng","year":"2025","journal-title":"Protein Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/bpa.12631","article-title":"Lysosomal cathepsin D is upregulated in Alzheimer\u2019s disease neocortex and may be a marker for neurofibrillary degeneration","volume":"29","author":"Chai","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/1873-3468.14549","article-title":"Senile plaques in Alzheimer\u2019s disease arise from A\u03b2- and cathepsin D-enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture","volume":"597","author":"Fu","year":"2023","journal-title":"FEBS Lett."},{"key":"ref_67","first-page":"10","article-title":"Cathepsin D: A candidate link between amyloid \u03b2-protein and tauopathy in Alzheimer disease","volume":"2","author":"Suire","year":"2021","journal-title":"J. Exp. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13195-024-01443-6","article-title":"Prominent tauopathy and intracellular \u03b2-amyloid accumulation triggered by genetic deletion of cathepsin D: Implications for Alzheimer disease pathogenesis","volume":"16","author":"Terron","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"989","DOI":"10.3233\/JAD-220852","article-title":"Serum cathepsin D is a potential biomarker for Alzheimer\u2019s disease dementia and cognitive decline","volume":"91","author":"Chai","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kim, J.W., Jung, S.Y., Kim, Y., Heo, H., Hong, C.H., Seo, S.W., Choi, S.H., Son, S.J., Lee, S., and Chang, J. (2021). Identification of cathepsin D as a plasma biomarker for Alzheimer\u2019s disease. Cells, 10.","DOI":"10.3390\/cells10010138"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0304-3940(00)01260-X","article-title":"The genetic association between cathepsin D and Alzheimer\u2019s disease","volume":"289","author":"Crawford","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1093\/aje\/kwh069","article-title":"Meta-analysis of the association of the cathepsin D Ala224Val gene polymorphism with the risk of Alzheimer\u2019s disease: A HuGE gene-disease association review","volume":"159","author":"Ntais","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.neurobiolaging.2009.10.011","article-title":"Cathepsin D gene and the risk of Alzheimer\u2019s disease: A population-based study and meta-analysis","volume":"32","author":"Schuur","year":"2011","journal-title":"Neurobiol. Aging."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neurobiolaging.2006.09.005","article-title":"Cathepsin D expression is decreased in Alzheimer\u2019s disease fibroblasts","volume":"29","author":"Urbanelli","year":"2008","journal-title":"Neurobiol. Aging."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chitranshi, N., Kumar, A., Sheriff, S., Gupta, V., Godinez, A., Saks, D., Sarkar, S., Shen, T., Mirzaei, M., and Basavarajappa, D. (2021). Identification of novel cathepsin B inhibitors with implications in Alzheimer\u2019s disease: Computational refining and biochemical evaluation. Cells, 10.","DOI":"10.3390\/cells10081946"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.neuron.2006.07.027","article-title":"Antiamyloidogenic and neuroprotective functions of cathepsin B: Implications for Alzheimer\u2019s disease","volume":"51","author":"Zhou","year":"2006","journal-title":"Neuron"},{"key":"ref_77","first-page":"1223","article-title":"Higher cathepsin B levels in plasma in Alzheimer\u2019s disease compared to healthy controls","volume":"22","author":"Hansson","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s40478-023-01632-8","article-title":"Cathepsin B abundance, activity and microglial localisation in Alzheimer\u2019s disease\u2013Down syndrome and early onset Alzheimer\u2019s disease; the role of elevated cystatin B","volume":"11","author":"Wu","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/s41386-024-01994-0","article-title":"Cathepsin B modulates microglial migration and phagocytosis of amyloid \u03b2 in Alzheimer\u2019s disease through PI3K-Akt signaling","volume":"50","author":"Jiang","year":"2025","journal-title":"Neuropsychopharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Hook, V., Yoon, M., Mosier, C., Ito, G., Podvin, S., Head, B.P., Rissman, R., O\u2019Donoghue, A.J., and Hook, G. (2020). Cathepsin B in neurodegeneration of Alzheimer\u2019s disease, traumatic brain injury, and related brain disorders. Biochim. Biophys. Acta Proteins Proteom., 1868.","DOI":"10.1016\/j.bbapap.2020.140428"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e13565","DOI":"10.1111\/acel.13565","article-title":"Microglial cathepsin E plays a role in neuroinflammation and amyloid \u03b2 production in Alzheimer\u2019s disease","volume":"21","author":"Xie","year":"2022","journal-title":"Aging Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e13531","DOI":"10.1111\/acel.13531","article-title":"Regulatory role of cathepsin L in induction of nuclear laminopathy in Alzheimer\u2019s disease","volume":"21","author":"Islam","year":"2022","journal-title":"Aging Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0304-3940(00)01326-4","article-title":"Expression of invariant chain and pro-cathepsin L in Alzheimer\u2019s brain","volume":"290","author":"Yoshiyama","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e14393","DOI":"10.1111\/acel.14393","article-title":"Neuronal cathepsin S increases neuroinflammation and causes cognitive decline via CX3CL1-CX3CR1 axis and JAK2-STAT3 pathway in aging and Alzheimer\u2019s disease","volume":"24","author":"Liu","year":"2025","journal-title":"Aging Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1002\/alz.13847","article-title":"Urolithin A improves Alzheimer\u2019s disease cognition and restores mitophagy and lysosomal functions","volume":"20","author":"Hou","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1177\/17474930241308142","article-title":"World Stroke Organization: Global Stroke Fact Sheet 2025","volume":"20","author":"Feigin","year":"2025","journal-title":"Int. J. Stroke"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12953-024-00236-x","article-title":"Multi-targeted Olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage","volume":"22","author":"Ding","year":"2024","journal-title":"Proteome Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12974-019-1398-3","article-title":"Cathepsin C promotes microglia M1 polarization and aggravates neuroinflammation via activation of Ca2+-dependent PKC\/p38MAPK\/NF-\u03baB pathway","volume":"16","author":"Liu","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/kjm2.12014","article-title":"Acute phase serum cathepsin S level and cathepsin S\/cystatin C ratio are the associated factors with cerebral infarction and their diagnostic value for cerebral infarction","volume":"35","author":"Zhang","year":"2019","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.bbi.2022.11.001","article-title":"Single-cell RNA sequencing of peripheral blood reveals that monocytes with high cathepsin S expression aggravate cerebral ischemia\u2013reperfusion injury","volume":"107","author":"Xie","year":"2023","journal-title":"Brain Behav. Immun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1161\/01.ATV.0000203526.75772.4b","article-title":"Destabilizing role of cathepsin S in murine atherosclerotic plaques","volume":"26","author":"Rodgers","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1172\/JCI200314915","article-title":"Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice","volume":"111","author":"Sukhova","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1161\/STROKEAHA.107.513648","article-title":"Cathepsin B, K, and S are expressed in cerebral aneurysms and promote the progression of cerebral aneurysms","volume":"39","author":"Aoki","year":"2008","journal-title":"Stroke"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s10571-019-00682-8","article-title":"Cathepsin K knockout exacerbates haemorrhagic transformation induced by recombinant tissue plasminogen activator after focal cerebral ischaemia in mice","volume":"39","author":"Zhao","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Lu, J., Li, H., Yu, Z., Cao, C., Xu, Z., Peng, L., Zhang, J.H., and Chen, G. (2024). Cathepsin B as a key regulator of ferroptosis in microglia following intracerebral hemorrhage. Neurobiol. Dis., 194.","DOI":"10.1016\/j.nbd.2024.106468"},{"key":"ref_96","first-page":"61","article-title":"Correlation of cathepsin S with coronary stenosis degree, carotid thickness, blood pressure, glucose and lipid metabolism and vascular endothelial function in atherosclerosis","volume":"19","author":"Huang","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e000353","DOI":"10.1136\/openhrt-2015-000353","article-title":"High levels of cathepsin D and cystatin B are associated with increased risk of coronary events","volume":"3","author":"Hultman","year":"2016","journal-title":"Open Heart"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"912","DOI":"10.3349\/ymj.2014.55.4.912","article-title":"Increased serum cathepsin K in patients with coronary artery disease","volume":"55","author":"Li","year":"2014","journal-title":"Yonsei Med. J."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Faraday, N., Schunke, K., Saleem, S., Fu, J., Wang, B., Zhang, J., Morrell, C., and Dore, S. (2013). Cathepsin G-dependent modulation of platelet thrombus formation in vivo by blood neutrophils. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071447"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1080\/15548627.2020.1761219","article-title":"Restoration of CTSD (cathepsin D) and lysosomal function in stroke is neuroprotective","volume":"17","author":"Hossain","year":"2021","journal-title":"Autophagy"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1007\/s00415-020-09836-x","article-title":"Heritable and non-heritable uncommon causes of stroke","volume":"268","author":"Bersano","year":"2021","journal-title":"J. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1212\/WNL.0000000000003251","article-title":"Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL)","volume":"87","author":"Bugiani","year":"2016","journal-title":"Neurology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/B978-0-323-99209-1.00018-1","article-title":"Monogenic causes of cerebral small vessel disease and stroke","volume":"204","author":"Guey","year":"2024","journal-title":"Handb. Clin. Neurol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s13760-019-01158-8","article-title":"Update on hereditary, autosomal dominant cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL)","volume":"119","author":"Finsterer","year":"2019","journal-title":"Acta Neurol. Belg."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e37297","DOI":"10.1097\/MD.0000000000037297","article-title":"Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment","volume":"103","author":"Haki","year":"2024","journal-title":"Medicine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"s53","DOI":"10.7861\/clinmedicine.16-6-s53","article-title":"Multiple sclerosis, a treatable disease","volume":"16","author":"Doshi","year":"2016","journal-title":"Clin. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/j.amjmed.2020.05.049","article-title":"Treatment of multiple sclerosis: A review","volume":"133","author":"Hauser","year":"2020","journal-title":"Am. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S1474-4422(22)00289-7","article-title":"Multiple sclerosis progression: Time for a new mechanism-driven framework","volume":"22","author":"Kuhlmann","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Pi\u0161lar, A., Bol\u010dina, L., and Kos, J. (2021). New insights into the role of cysteine cathepsins in neuroinflammation. Biomolecules, 11.","DOI":"10.3390\/biom11121796"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Stoka, V., Vasiljeva, O., Nakanishi, H., and Turk, V. (2023). The role of cysteine protease cathepsins B, H, C, and X\/Z in neurodegenerative diseases and cancer. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202307.1708.v1"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1111\/j.1582-4934.2010.01229.x","article-title":"Cathepsins and their endogenous inhibitors cystatins: Expression and modulation in multiple sclerosis","volume":"15","author":"Paperna","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12974-017-0874-x","article-title":"A role for cathepsin Z in neuroinflammation provides mechanistic support for an epigenetic risk factor in multiple sclerosis","volume":"14","author":"Allan","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Allan, E.R., and Yates, R.M. (2015). Redundancy between cysteine cathepsins in murine experimental autoimmune encephalomyelitis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128945"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Holm Nielsen, S., Karsdal, M., Manoel, B., Bay-Jensen, A.C., and Henriksen, K. (2024). Diagnostic potential of blood-based biomarkers in multiple sclerosis. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1425046"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/mds.29228","article-title":"Prevalence and incidence of Huntington\u2019s disease: An updated systematic review and meta-analysis","volume":"37","author":"Medina","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Drobny, A., Prieto Huarcaya, S., Dobert, J., Kluge, A., Bunk, J., Schlothauer, T., and Zunke, F. (2022). The role of lysosomal cathepsins in neurodegeneration: Mechanistic insights, diagnostic potential and therapeutic approaches. Biochim. Biophys. Acta Mol. Cell Res., 1869.","DOI":"10.1016\/j.bbamcr.2022.119243"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1091\/mbc.12.5.1393","article-title":"Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation","volume":"12","author":"Waelter","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington\u2019s disease","volume":"369","author":"Walker","year":"2007","journal-title":"Lancet"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/00005072-198511000-00003","article-title":"Neuropathological classification of Huntington\u2019s disease","volume":"44","author":"Vonsattel","year":"1985","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"17471","DOI":"10.1074\/jbc.M112.352781","article-title":"Cathepsins L and Z are critical in degrading polyglutamine-containing proteins within lysosomes","volume":"287","author":"Bhutani","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.nbd.2005.11.012","article-title":"Lysosomal proteases are involved in generation of N-terminal huntingtin fragments","volume":"22","author":"Kim","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1750-1326-6-37","article-title":"Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons","volume":"6","author":"Liang","year":"2011","journal-title":"Mol. Neurodegener."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s13312-025-00120-7","article-title":"ILAE 2025 Classification of Epileptic Seizures: Key Revisions and Implications for Clinical Practice","volume":"62","author":"Ragunathan","year":"2025","journal-title":"Indian Pediatr."},{"key":"ref_124","first-page":"S29","article-title":"Status epilepticus: Mechanisms of brain damage and rational management","volume":"23","author":"Bajorek","year":"1982","journal-title":"Epilepsia"},{"key":"ref_125","unstructured":"GBD Epilepsy Collaborators (2025). Global, regional, and national burden of epilepsy, 1990\u20132021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet Public Health, 10, e203\u2013e227."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1528-1167.2007.01422.x","article-title":"Molecular background of EPM1\u2013Unverricht-Lundborg disease","volume":"49","author":"Joensuu","year":"2008","journal-title":"Epilepsia"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/B978-0-444-52891-9.00069-5","article-title":"Myoclonus and epilepsy","volume":"111","author":"Guerrini","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"5910","DOI":"10.1523\/JNEUROSCI.0682-09.2009","article-title":"Cystatin B deficiency sensitizes neurons to oxidative stress in progressive myoclonus epilepsy, EPM1","volume":"29","author":"Lehtinen","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1124\/pharmrev.121.000527","article-title":"Cathepsin B gene knockout improves behavioral deficits and reduces pathology in models of neurologic disorders","volume":"74","author":"Hook","year":"2022","journal-title":"Pharmacol. Rev."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/neu.10253","article-title":"Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1)","volume":"56","author":"Houseweart","year":"2003","journal-title":"J. Neurobiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1046\/j.1460-9568.2000.00058.x","article-title":"Seizures induce widespread upregulation of cystatin B, the gene mutated in progressive myoclonus epilepsy, in rat forebrain neurons","volume":"12","author":"Kokaia","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/jnr.22338","article-title":"Nuclear translocation of mitochondrial cytochrome c, lysosomal cathepsins B and D, and three other death-promoting proteins within the first 60 minutes of generalized seizures","volume":"88","author":"Zhao","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1528-1167.2007.01290.x","article-title":"Dynamic changes of proteases and protease inhibitors revealed by microarray analysis in CA3 and entorhinal cortex during epileptogenesis in the rat","volume":"48","author":"Gorter","year":"2007","journal-title":"Epilepsia"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S1474-4422(21)00465-8","article-title":"Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_135","doi-asserted-by":"crossref","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":"ref_136","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1097\/WCO.0000000000000730","article-title":"Epidemiology of amyotrophic lateral sclerosis: An update of recent literature","volume":"32","author":"Longinetti","year":"2019","journal-title":"Curr. Opin. Neurol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e075037","DOI":"10.1136\/bmj-2023-075037","article-title":"Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis","volume":"383","author":"Ilieva","year":"2023","journal-title":"BMJ"},{"key":"ref_138","first-page":"57","article-title":"Variation in worldwide incidence of amyotrophic lateral sclerosis: A meta-analysis","volume":"46","author":"Marin","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"E1453","DOI":"10.1503\/cmaj.191721","article-title":"Canadian best practice recommendations for the management of amyotrophic lateral sclerosis","volume":"192","author":"Shoesmith","year":"2020","journal-title":"CMAJ"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jns.2017.11.023","article-title":"Co-localization of cystatin C and prosaposin in cultured neurons and in anterior horn neurons with amyotrophic lateral sclerosis","volume":"384","author":"Wada","year":"2018","journal-title":"J. Neurol. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4768","DOI":"10.1007\/s12035-023-03835-5","article-title":"Lnc-HIBADH-4 regulates autophagy-lysosome pathway in amyotrophic lateral sclerosis by targeting cathepsin D","volume":"61","author":"Huang","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.ajhg.2020.04.007","article-title":"Characterizing the causal pathway for genetic variants associated with neurological phenotypes using human brain-derived proteome data","volume":"106","author":"Kibinge","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"885","DOI":"10.3389\/fneur.2015.00178","article-title":"Cathepsin B Is a New Drug Target for Traumatic Brain Injury Therapeutics: Evidence for E64d as a Promising Lead Drug Candidate","volume":"6","author":"Hook","year":"2015","journal-title":"Front. Neurol."},{"key":"ref_144","first-page":"1","article-title":"Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice","volume":"2013","author":"Xu","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3390\/pathophysiology31030035","article-title":"Advances in Cathepsin S Inhibition: Challenges and Breakthroughs in Drug Development","volume":"31","author":"Ajani","year":"2024","journal-title":"Pathophysiology"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3644","DOI":"10.1093\/rheumatology\/kead092","article-title":"A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study on the Effects of a Cathepsin S Inhibitor in Primary Sj\u00f6gren\u2019s Syndrome","volume":"62","author":"Bentley","year":"2023","journal-title":"Rheumatology"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Ma, L., Wu, S., Gusdon, A.M., Chen, H., Hu, H., Paz, A.S., Aronowski, J., Savarraj, J.P., Kitagawa, R.S., and Choi, H.A. (2022). Cathepsin L and Acute Ischemic Stroke: A Mini-Review. Front. Stroke, 1.","DOI":"10.3389\/fstro.2022.1050536"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s11010-016-2924-6","article-title":"Clinical Significance of Cathepsin L and Cathepsin B in Dilated Cardiomyopathy","volume":"428","author":"Mehra","year":"2017","journal-title":"Mol. Cell. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:28:19Z","timestamp":1760034499000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":148,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26167886"],"URL":"https:\/\/doi.org\/10.3390\/ijms26167886","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]}}}