Molecular background of EPM1—Unverricht–Lundborg disease

2007/11/20 by Tarja Joensuu, Anna‐Elina Lehesjoki, Outi Kopra · 27 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Glycogen Storage Diseases and Myoclonus #Genetics and Neurodevelopmental Disorders #Amino Acid Enzymes and Metabolism

paper · pdf · doi:10.1111/j.1528-1167.2007.01422.x

Abstract

Unverricht-Lundborg disease (EPM1) is an autosomal recessively inherited neurodegenerative disorder and the most common single cause of progressive myoclonus epilepsy worldwide. Mutations in the gene encoding cystatin B (CSTB), a cysteine protease inhibitor, are responsible for the primary defect underlying EPM1. Here, progress toward understanding the molecular mechanisms in EPM1 is reviewed. We summarize the current knowledge about the CSTB gene and mutations as well as the cellular biology of the CSTB protein with emphasis on data emerging from analysis of EPM1 patients. We shed light on the disease mechanisms of EPM1 based on characterization of the CSTB-deficient mouse model.

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• Photosensitivity in Lafora and Unverricht–Lundborg progressive myoclonic epilepsies
• Transcriptomic and proteomic insights into progressive myoclonus epilepsy type 1
• Cystatin B deficiency sensitizes neurons to oxidative stress in progressive myoclonus epilepsy, EPM1. [europepmc]
• Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis. [europepmc]
• Human stefin B normal and patho-physiological role: molecular and cellular aspects of amyloid-type aggregation of certain EPM1 mutants. [europepmc]
• Innate Immune Response in Brain, NF-Kappa B Signaling and Cystatins. [europepmc]
• The Role of Stefin B in Neuro-inflammation. [europepmc]
• Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation. [europepmc]
• Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy. [europepmc]
• Possible Mechanisms by which Stefin B could Regulate Proteostasis and Oxidative Stress. [europepmc]
• Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids. [europepmc]
• The best evidence for progressive myoclonic epilepsy: A pathway to precision therapy. [europepmc]
• Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages. [europepmc]
• Cystatin B is essential for proliferation and interneuron migration in individuals with EPM1 epilepsy. [europepmc]
• Microglial phagocytosis dysfunction in the dentate gyrus is related to local neuronal activity in a genetic model of epilepsy. [europepmc]
• Quantitative Changes in the Mitochondrial Proteome of Cerebellar Synaptosomes From Preclinical Cystatin B-Deficient Mice. [europepmc]
• Synergy of the Inhibitory Action of Polyphenols Plus Vitamin C on Amyloid Fibril Formation: Case Study of Human Stefin B. [europepmc]
• Cognitive Dysfunction in Repeat Expansion Diseases: A Review. [europepmc]
• Evaluation of CSTB and DMBT1 expression in saliva of gastric cancer patients and controls. [europepmc]
• Human stefin B: from its structure, folding, and aggregation to its function in health and disease. [europepmc]
• Insights into the Genetic Profile of Two Siblings Affected by Unverricht-Lundborg Disease Using Patient-Derived hiPSCs. [europepmc]
• Progressive mitochondrial dysfunction in cerebellar synaptosomes of cystatin B-deficient mice. [europepmc]
• Progressive myoclonic epilepsy type 1 (EPM1) patients present with abnormal 1 H MRS brain metabolic profiles associated with cognitive function. [europepmc]
• ILAE Genetics Literacy series: Progressive myoclonus epilepsies. [europepmc]
• Pathological Deficit of Cystatin B Impairs Synaptic Plasticity in EPM1 Human Cerebral Organoids. [europepmc]
• The Roles of Cystatin B in the Brain and Pathophysiological Mechanisms of Progressive Myoclonic Epilepsy Type 1. [europepmc]
• Cathepsins in Neurological Diseases. [europepmc]

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