Transcriptomic and proteomic insights into progressive myoclonus epilepsy type 1.

Overview

Authors: Alina Malyutina^1,2, Carina Lund^1,3, Saara Tegelberg^1,3, Paula Hakala^1,3, Tuula A Nyman⁴, Anna-Elina Lehesjoki^1,3, Tarja Joensuu^1,3

ORCID iDs: Alina Malyutina, Carina Lund, Saara Tegelberg, Tuula A Nyman, Anna-Elina Lehesjoki, Tarja Joensuu

Institutions: Orion Corporation (Finland) (Finland); Folkhälsans Forskningscentrum (Finland); University of Helsinki (Finland); Oslo University Hospital (Norway); University of Oslo (Norway)

Journal: Disease models & mechanisms, volume 19, issue 4, article dmm052681

Dates: received 25 September 2025; accepted 22 February 2026; published online 5 May 2026; in print April 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1242/dmm.052681 · PMID 41782446 · PMCID PMC13225231 · OpenAlex W7133988320

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: genetics / omics (modality), mouse (organism), epilepsy (population)

Methods: Statistics

Keywords: EPM1, Cystatin B, Cstb−/− mouse, Brain, Transcriptomics, Proteomics

MeSH: Myoclonic Epilepsies, Progressive*, Proteome*, Proteomics*, Transcriptome*, Animals, Biomarkers, Brain, Cerebellum, Cystatin B, Gene Expression Profiling, Gene Expression Regulation, Lysosomes, Mitochondria (* major topic)

Topic: Glycogen Storage Diseases and Myoclonus (Rheumatology, Medicine), according to OpenAlex

Funding: Medicinska Understadsfareningen Liv och Halsa; Helsingin Yliopisto; Norges Forskningsrad (295910); Business Finland; Sigrid Juséliuksen Säätiö; Sigrid Juseliuksen Saati; Finska Lakaresallskapet; Folkhalsanin Tutkimussaati; Folkhälsanin Tutkimussäätiö; Medicinska Understödsföreningen Liv och Hälsa; Finska Läkaresällskapet

Citations: not cited yet (Europe PMC); 116 references in the paper

Abstract

Progressive myoclonus epilepsy type 1 (EPM1) is a rare neurodegenerative disease caused by partial loss of function of cystatin B (CSTB), a cysteine protease inhibitor with known neuroprotective roles. 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−/−) mouse brain – the cerebellum, cerebral cortex and hippocampus – 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.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

geo:GSE309108, at NCBI GEO; found in the text, “Footnotes”

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 6 keywords, 13 MeSH terms, 11 funders, 115 references.

Cite

This paper

Malyutina, A., Lund, C., Tegelberg, S., Hakala, P., Nyman, T. A., Lehesjoki, A.-E., & Joensuu, T. (2026). Transcriptomic and proteomic insights into progressive myoclonus epilepsy type 1. Disease models & mechanisms, 19(4), dmm052681. https://doi.org/10.1242/dmm.052681

BibTeX

@article{malyutina2026transcriptomic, author = {Malyutina, Alina and Lund, Carina and Tegelberg, Saara and Hakala, Paula and Nyman, Tuula A and Lehesjoki, Anna-Elina and Joensuu, Tarja}, title = {{Transcriptomic and proteomic insights into progressive myoclonus epilepsy type 1}}, journal = {Disease models \& mechanisms}, year = {2026}, month = apr, volume = {19}, number = {4}, pages = {dmm052681}, publisher = {Company of Biologists}, issn = {1754-8403}, doi = {10.1242/dmm.052681}, url = {https://doi.org/10.1242/dmm.052681}, pmid = {41782446}, pmcid = {PMC13225231} }

RIS

TY - JOUR AU - Malyutina, Alina AU - Lund, Carina AU - Tegelberg, Saara AU - Hakala, Paula AU - Nyman, Tuula A AU - Lehesjoki, Anna-Elina AU - Joensuu, Tarja TI - Transcriptomic and proteomic insights into progressive myoclonus epilepsy type 1 T2 - Disease models & mechanisms J2 - Dis Model Mech PY - 2026 DA - 2026/04/01 VL - 19 IS - 4 SP - dmm052681 SN - 1754-8403 PB - Company of Biologists DO - 10.1242/dmm.052681 UR - https://doi.org/10.1242/dmm.052681 LA - en ER -

CSL-JSON

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