Transcriptomic and proteomic insights into progressive myoclonus epilepsy type 1.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Progressive myoclonus epilepsy type 1 (EPM1) is a rare neurodegenerative disorder.
• It results from partial loss of function of cystatin B (CSTB), a neuroprotective protein.
• Current treatments for EPM1 symptoms are lacking.

Purpose of the Study:

• To investigate the molecular consequences of CSTB loss in the brain.
• To identify potential therapeutic targets and biomarkers for EPM1.

Main Methods:

• Comparative transcriptome and proteome analysis in CSTB-deficient (Cstb-/-) mouse brain regions (cerebellum, cerebral cortex, hippocampus).
• Analysis focused on disease progression stages.

Main Results:

• Upregulation of immune response genes across all analyzed brain regions.
• Downregulation of oxidative phosphorylation and differential expression of mitochondrial genes, particularly in the cerebellum, indicating impaired energy metabolism.
• Upregulation of lysosomal function genes alongside downregulation of genes for lysosomal acidification, suggesting lysosomal dysfunction.
• Identification of clusterin, apolipoprotein E, peroxiredoxin 6, cathepsin D, and aldolase C as potential progression biomarkers.

Conclusions:

• CSTB deficiency profoundly affects immune response, energy metabolism, and lysosomal function in the brain.
• These pathways represent promising therapeutic targets for EPM1.
• Identified proteins may serve as biomarkers for disease progression.