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The disease mechanisms remain largely unsolved, and no treatments are available to control the debilitating myoclonus in EPM1. We investigated the impact of CSTB loss on transcriptome and proteome in three regions of CSTB-deficient (Cstb\u2212\/\u2212) mouse brain \u2013 the cerebellum, cerebral cortex and hippocampus \u2013 during disease progression, providing comprehensive insights into the molecular changes and disease mechanisms. We elucidated three critical pathways as potential therapeutic targets. First, significant upregulation of immune response genes indicates heightened immune activity across all brain regions. Second, consistent downregulation of the oxidative phosphorylation pathway with differential expression of mitochondrial genes implies impaired energy metabolism primarily affecting the cerebellum. Third, upregulation of genes essential for lysosomal function with simultaneous downregulation of genes encoding proteins crucial for lysosomal acidification suggests lysosomal dysfunction as an essential pathogenetic mechanism. By combining proteome with transcriptome data, we identified clusterin, apolipoprotein E, peroxiredoxin 6, cathepsin D and aldolase C as potential biomarkers for disease progression.<\/jats:p>","DOI":"10.1242\/dmm.052681","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T08:06:01Z","timestamp":1772697961000},"source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic and proteomic insights into progressive myoclonus epilepsy type 1"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8220-5859","authenticated-orcid":false,"given":"Alina","family":"Malyutina","sequence":"first","affiliation":[{"name":"Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"Orion Corporation 3 , 02200 Espoo ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9050-3626","authenticated-orcid":false,"given":"Carina","family":"Lund","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 2 Medicum, Faculty of Medicine , , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5682-4787","authenticated-orcid":false,"given":"Saara","family":"Tegelberg","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 2 Medicum, Faculty of Medicine , , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Hakala","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 2 Medicum, Faculty of Medicine , , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8787-5886","authenticated-orcid":false,"given":"Tuula A.","family":"Nyman","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo and Oslo University Hospital 4 Department of Immunology , , 0372 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-3113","authenticated-orcid":false,"given":"Anna-Elina","family":"Lehesjoki","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 2 Medicum, Faculty of Medicine , , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-2141","authenticated-orcid":false,"given":"Tarja","family":"Joensuu","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center 1 , 00290 Helsinki ,","place":["Finland"]},{"name":"University of Helsinki 2 Medicum, Faculty of Medicine , , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"2026050506474892900_DMM052681C1","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1111\/cge.14720","article-title":"Delineating the clinical and brain imaging characteristics of the neonatal form of CSTB-related neurodevelopmental disorders","volume":"108","author":"Abdel-Hamid","year":"2025","journal-title":"Clin. 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