{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:48:36Z","timestamp":1790999316361,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Eastern Finland","award":["101034307"],"award-info":[{"award-number":["101034307"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessive disorder, also known as Unverricht\u2013Lundborg disease (ULD). EPM1 patients suffer from photo-sensitive seizures, stimulus-sensitive myoclonus, nocturnal myoclonic seizures, ataxia and dysarthria. In addition, cerebral ataxia and impaired GABAergic inhibition are typically present. EPM1 is caused by mutations in the Cystatin B gene (CSTB). The CSTB protein functions as an intracellular thiol protease inhibitor and inhibits Cathepsin function. It also plays a crucial role in brain development and regulates various functions in neurons beyond maintaining cellular proteostasis. These include controlling cell proliferation and differentiation, synaptic functions and protection against oxidative stress, likely through regulation of mitochondrial function. Depending on the differentiation stage and status of neurons, the protein localizes either to the cytoplasm, nucleus, lysosomes or mitochondria. Further, CSTB can also be secreted to the extracellular matrix for interneuron rearrangement and migration. In this review, we will review the various functions of CSTB in the brain and discuss the putative pathophysiological mechanism underlying EPM1.<\/jats:p>","DOI":"10.3390\/cells13020170","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T08:12:37Z","timestamp":1705392757000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Roles of Cystatin B in the Brain and Pathophysiological Mechanisms of Progressive Myoclonic Epilepsy Type 1"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-6225","authenticated-orcid":false,"given":"Shekhar","family":"Singh","sequence":"first","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5102-0672","authenticated-orcid":false,"given":"Riikka H.","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1212\/WNL.42.8.1545","article-title":"Linkage studies in progressive myoclonus epilepsy: Unverricht-Lundborg and Lafora\u2019s diseases","volume":"42","author":"Lehesjoki","year":"1992","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.seizure.2019.08.012","article-title":"The best evidence for progressive myoclonic epilepsy: A pathway to precision therapy","volume":"71","author":"Orsini","year":"2019","journal-title":"Seizure"},{"key":"ref_3","first-page":"e3117","article-title":"Unverricht-Lundborg disease (EPM1) in Finland: A nationwide population-based study","volume":"95","year":"2020","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1528-1167.2008.01546.x","article-title":"Clinical picture of EPM1-Unverricht-Lundborg disease","volume":"49","author":"Khyuppenen","year":"2008","journal-title":"Epilepsia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/sj.ejhg.5201300","article-title":"Loss of lysosomal association of cystatin B proteins representing progressive myoclonus epilepsy, EPM1, mutations","volume":"13","author":"Alakurtti","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0006-291X(03)01386-X","article-title":"Cystatin-B is expressed by neural stem cells and by differentiated neurons and astrocytes","volume":"308","author":"Hjelm","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1093\/hmg\/11.23.2941","article-title":"New insights into the molecular basis of progressive myoclonus epilepsy: A multiprotein complex with cystatin B","volume":"11","author":"Riccio","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"570640","DOI":"10.3389\/fnmol.2020.570640","article-title":"Quantitative Changes in the Mitochondrial Proteome of Cerebellar Synaptosomes From Preclinical Cystatin B-Deficient Mice","volume":"13","author":"Gorski","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e11419","DOI":"10.15252\/emmm.201911419","article-title":"Cystatin B is essential for proliferation and interneuron migration in individuals with EPM1 epilepsy","volume":"12","author":"Pipicelli","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/glia.22760","article-title":"Abnormal microglial activation in the Cstb(-\/-) mouse, a model for progressive myoclonus epilepsy, EPM1","volume":"63","author":"Okuneva","year":"2015","journal-title":"Glia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1111\/j.1528-1167.2012.03718.x","article-title":"Electroclinical presentation and genotype-phenotype relationships in patients with Unverricht-Lundborg disease carrying compound heterozygous CSTB point and indel mutations","volume":"53","author":"Canafoglia","year":"2012","journal-title":"Epilepsia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1528-1167.2007.01422.x","article-title":"Molecular background of EPM1-Unverricht-Lundborg disease","volume":"49","author":"Joensuu","year":"2008","journal-title":"Epilepsia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.eplepsyres.2011.11.004","article-title":"Unverricht-Lundborg disease: Homozygosity for a new splicing mutation in the cystatin B gene","volume":"99","author":"Pinto","year":"2012","journal-title":"Epilepsy Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/386847a0","article-title":"Dodecamer repeat expansion in cystatin B gene in progressive myoclonus epilepsy","volume":"386","author":"Lalioti","year":"1997","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1056\/NEJMoa1515792","article-title":"Exome Sequencing and the Management of Neurometabolic Disorders","volume":"374","author":"Shyr","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1126\/science.271.5256.1731","article-title":"Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1)","volume":"271","author":"Pennacchio","year":"1996","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/ng0397-298","article-title":"Unstable insertion in the 5\u2019 flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1","volume":"15","author":"Rochefort","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_18","first-page":"342","article-title":"Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1)","volume":"60","author":"Lalioti","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_19","unstructured":"Adam, M.P., Feldman, J., and Mirzaa, G.M. (2023, November 01). Progressive Myoclonic Epilepsy Type 1. 2004 Jun 24 [Updated 2 July 2020], GeneReviews\u00ae [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1142."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/sj.ejhg.5201723","article-title":"Cystatin B: Mutation detection, alternative splicing and expression in progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients","volume":"15","author":"Joensuu","year":"2007","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/s41436-019-0624-9","article-title":"Correction: Sherloc: A comprehensive refinement of the ACMG-AMP variant classification criteria","volume":"22","author":"Nykamp","year":"2020","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0887-8994(01)00336-8","article-title":"Unverricht-Lundborg disease with cystatin B gene abnormalities","volume":"26","author":"Imai","year":"2002","journal-title":"Pediatr. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41431-017-0034-x","article-title":"Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy","volume":"26","author":"Bobbili","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/j.0013-9580.2004.43703.x","article-title":"Univerricht-Lundborg disease: Underdiagnosed in the Netherlands","volume":"45","author":"Halley","year":"2004","journal-title":"Epilepsia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/ejhg.2017.39","article-title":"Severe neurodegeneration, progressive cerebral volume loss and diffuse hypomyelination associated with a homozygous frameshift mutation in CSTB","volume":"25","author":"Marshall","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/(SICI)1096-8628(19970919)74:5<467::AID-AJMG1>3.0.CO;2-L","article-title":"Novel cystatin B mutation and diagnostic PCR assay in an Unverricht-Lundborg progressive myoclonus epilepsy patient","volume":"74","author":"Bespalova","year":"1997","journal-title":"Am. J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1212\/WNL.57.6.1050","article-title":"Unverricht-Lundborg disease in a five-generation Arab family: Instability of dodecamer repeats","volume":"57","author":"Mazarib","year":"2001","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1093\/hmg\/8.11.1985","article-title":"Instability of the EPM1 minisatellite","volume":"8","author":"Larson","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1001\/archneur.57.8.1199","article-title":"A patient with 2 different repeat expansion mutations","volume":"57","author":"Nokelainen","year":"2000","journal-title":"Arch. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1111\/ane.13706","article-title":"Comorbidities in patients with Unverricht-Lundborg disease (EPM1)","volume":"146","year":"2022","journal-title":"Acta Neurol. Scand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/S0140-6736(83)90749-3","article-title":"\u201cBaltic\u201d myoclonus epilepsy: Hereditary disorder of childhood made worse by phenytoin","volume":"2","author":"Eldridge","year":"1983","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1111\/j.1528-1157.1991.tb05549.x","article-title":"Clinical and neurophysiological development of Unverricht-Lundborg disease in four Swedish siblings","volume":"32","author":"Kyllerman","year":"1991","journal-title":"Epilepsia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1212\/01.WNL.0000147475.71345.AA","article-title":"Sensorimotor cortex excitability in Unverricht-Lundborg disease and Lafora body disease","volume":"63","author":"Canafoglia","year":"2004","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Joensuu, T., Tegelberg, S., Reinmaa, E., Segerstr\u00e5le, M., Hakala, P., Pehkonen, H., Korpi, E.R., Tyynel\u00e4, J., Taira, T., and Hovatta, I. (2014). Gene expression alterations in the cerebellum and granule neurons of Cstb(-\/-) mouse are associated with early synaptic changes and inflammation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089321"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1399-0004.1979.tb01770.x","article-title":"Progressive myoclonus epilepsy: Genetic and nosological aspects with special reference to 107 Finnish patients","volume":"15","author":"Norio","year":"1979","journal-title":"Clin. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1212\/WNL.58.11.1686","article-title":"Brainstem involvement in Unverricht-Lundborg disease (EPM1): An MRI and (1)H MRS study","volume":"58","author":"Mascalchi","year":"2002","journal-title":"Neurology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/epi.17466","article-title":"Short- and long-interval intracortical inhibition in EPM1 is related to genotype","volume":"64","author":"Silvennoinen","year":"2023","journal-title":"Epilepsia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ng0497-393","article-title":"Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1","volume":"15","author":"Virtaneva","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1212\/WNL.0000000000001466","article-title":"Refining the phenotype of Unverricht-Lundborg disease (EPM1): A population-wide Finnish study","volume":"84","author":"Joensuu","year":"2015","journal-title":"Neurology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0014-5793(88)80541-6","article-title":"Cloning a synthetic gene for human stefin B and its expression in E. coli","volume":"239","author":"Jerala","year":"1988","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.bbamcr.2007.08.007","article-title":"Cystatin B and its EPM1 mutants are polymeric and aggregate prone in vivo","volume":"1783","author":"Cipollini","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1009976","DOI":"10.3389\/fnmol.2022.1009976","article-title":"Human stefin B: From its structure, folding, and aggregation to its function in health and disease","volume":"15","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_43","first-page":"458","article-title":"The Role of Stefin B in Neuro-inflammation","volume":"9","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.nbd.2005.02.012","article-title":"Cell-specific expression of the epm1 (cystatin B) gene in developing rat cerebellum","volume":"20","author":"Riccio","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/3059","article-title":"Progressive ataxia, myoclonic epilepsy and cerebellar apoptosis in cystatin B-deficient mice","volume":"20","author":"Pennacchio","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3389\/fnmol.2019.00195","article-title":"Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids","volume":"12","author":"Penna","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1006\/excr.2000.5085","article-title":"Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonus epilepsy (EPM1)","volume":"262","author":"Riccio","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1006\/excr.1999.4479","article-title":"Characterization of NF-L and betaIISigma1-spectrin interaction in live cells","volume":"250","author":"Macioce","year":"1999","journal-title":"Exp. Cell Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1074\/jbc.273.4.2379","article-title":"Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit","volume":"273","author":"Liliental","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_51","first-page":"221","article-title":"Progressive myoclonic epilepsy: Anatomo-clinical study of a sporadic case with a marked cerebellar symptomatology (author\u2019s transl)","volume":"96","author":"Nardelli","year":"1975","journal-title":"Riv. Patol. Nerv. Ment."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1111\/epi.16692","article-title":"Microglial phagocytosis dysfunction in the dentate gyrus is related to local neuronal activity in a genetic model of epilepsy","volume":"61","author":"Bonifazi","year":"2020","journal-title":"Epilepsia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/j.1528-1167.2007.00985.x","article-title":"Seizures, ataxia, and neuronal loss in cystatin B heterozygous mice","volume":"48","author":"Kaasik","year":"2007","journal-title":"Epilepsia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1148\/radiol.13122458","article-title":"White matter degeneration with Unverricht-Lundborg progressive myoclonus epilepsy: A translational diffusion-tensor imaging study in patients and cystatin B-deficient mice","volume":"269","author":"Manninen","year":"2013","journal-title":"Radiology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/NEN.0b013e31823e68e1","article-title":"Early microglial activation precedes neuronal loss in the brain of the Cstb-\/- mouse model of progressive myoclonus epilepsy, EPM1","volume":"71","author":"Tegelberg","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.nbd.2012.04.005","article-title":"Loss of cortical GABA terminals in Unverricht-Lundborg disease","volume":"47","author":"Buzzi","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10078","DOI":"10.1074\/jbc.M109.034793","article-title":"Stefin B interacts with histones and cathepsin L in the nucleus","volume":"285","author":"Konjar","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1128\/MCB.26.2.489-501.2006","article-title":"H2A.Z functions to regulate progression through the cell cycle","volume":"26","author":"Dhillon","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1101\/gad.1547707","article-title":"Nucleosome stability mediated by histone variants H3.3 and H2A.Z","volume":"21","author":"Jin","year":"2007","journal-title":"Genes Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/bss0700179","article-title":"Cystatins","volume":"70","author":"Abrahamson","year":"2003","journal-title":"Biochem. Soc. Symp."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1097-2765(04)00209-6","article-title":"A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP\/Cux transcription factor","volume":"14","author":"Goulet","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1128\/MCB.26.6.2441-2455.2006","article-title":"The p110 isoform of the CDP\/Cux transcription factor accelerates entry into S phase","volume":"26","author":"Sansregret","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/ncomms1204","article-title":"Structural basis for the recognition and cleavage of histone H3 by cathepsin L.","volume":"2","author":"Krupa","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5210","DOI":"10.1038\/ncomms6210","article-title":"Histone H3.3 and its proteolytically processed form drive a cellular senescence programme","volume":"5","author":"Duarte","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.cell.2008.09.055","article-title":"Cathepsin L proteolytically processes histone H3 during mouse embryonic stem cell differentiation","volume":"135","author":"Duncan","year":"2008","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Daura, E., Tegelberg, S., Yoshihara, M., Jackson, C., Simonetti, F., Aksentjeff, K., Ezer, S., Hakala, P., Katayama, S., and Kere, J. (2021). Cystatin B-deficiency triggers ectopic histone H3 tail cleavage during neurogenesis. Neurobiol. Dis., 156.","DOI":"10.1016\/j.nbd.2021.105418"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0378-1119(99)00550-8","article-title":"Characterization of the cystatin B gene promoter harboring the dodecamer repeat expanded in progressive myoclonus epilepsy, EPM1","volume":"242","author":"Alakurtti","year":"2000","journal-title":"Gene"},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"1175851","DOI":"10.3389\/fnmol.2023.1175851","article-title":"Progressive mitochondrial dysfunction in cerebellar synaptosomes of cystatin B-deficient mice","volume":"16","author":"Gorski","year":"2023","journal-title":"Front. Mol. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1146\/annurev-immunol-032713-120240","article-title":"Microglia development and function","volume":"32","author":"Nayak","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/j.1471-4159.2009.06494.x","article-title":"C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production","volume":"112","author":"Fraser","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1093\/hmg\/10.18.1867","article-title":"Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes","volume":"10","author":"Lieuallen","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_73","first-page":"376","article-title":"Neuroprotective role of fibronectin in neuron-glial extrasynaptic transmission","volume":"8","author":"Wang","year":"2013","journal-title":"Neural Regen. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tins.2015.04.003","article-title":"Glial fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker","volume":"38","author":"Yang","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1126\/science.7914033","article-title":"A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells","volume":"265","author":"Han","year":"1994","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1152\/jn.1995.74.4.1473","article-title":"GABA receptors precede glutamate receptors in hypothalamic development; differential regulation by astrocytes","volume":"74","author":"Chen","year":"1995","journal-title":"J. Neurophysiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s11011-014-9560-1","article-title":"GABA receptors in brain development, function, and injury","volume":"30","author":"Wu","year":"2015","journal-title":"Metab. Brain Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1152\/jn.00204.2010","article-title":"A dynamic role for GABA receptors on the firing pattern of midbrain dopaminergic neurons","volume":"104","author":"Lobb","year":"2010","journal-title":"J. Neurophysiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.nbd.2006.11.006","article-title":"A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression","volume":"25","author":"Franceschetti","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/0092-8674(95)90538-3","article-title":"The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors","volume":"81","author":"Okada","year":"1995","journal-title":"Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/2\/170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:48:09Z","timestamp":1760104089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/2\/170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":80,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cells13020170"],"URL":"https:\/\/doi.org\/10.3390\/cells13020170","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,16]]}}}