Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myoclonus-dystonia syndrome (MDS) is a genetically heterogeneous disorder characterized by myoclonic jerks often seen in combination with dystonia and psychiatric co-morbidities and epilepsy. Mutations in the gene encoding epsilon-sarcoglycan (SGCE) have been found in some patients with MDS. SGCE is a maternally imprinted gene with the disease being inherited in an autosomal dominant pattern with reduced penetrance upon maternal transmission. In the central nervous system, epsilon-sarcoglycan is widely expressed in neurons of the cerebral cortex, basal ganglia, hippocampus, cerebellum and the olfactory bulb. epsilon-Sarcoglycan is located at the plasma membrane in neurons, muscle and transfected cells. To determine the effect of MDS-associated mutations on the function of epsilon-sarcoglycan we examined the biosynthesis and trafficking of wild-type and mutant proteins in cultured cells. In contrast to the wild-type protein, disease-associated epsilon-sarcoglycan missense mutations (H36P, H36R and L172R) produce proteins that are undetectable at the cell surface and are retained intracellularly. These mutant proteins become polyubiquitinated and are rapidly degraded by the proteasome. Furthermore, torsinA, that is mutated in DYT1 dystonia, a rare type of primary dystonia, binds to and promotes the degradation of epsilon-sarcoglycan mutants when both proteins are co-expressed. These data demonstrate that some MDS-associated mutations in SGCE impair trafficking of the mutant protein to the plasma membrane and suggest a role for torsinA and the ubiquitin proteasome system in the recognition and processing of misfolded epsilon-sarcoglycan.
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PMID:SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA. 1720 Jan 51

Intracellular transport, processing and stability of mRNA play critical roles in the functional physiology of the cell and defects in these processes are thought to underlie the pathogenesis in a number of neurodegenerative disorders. One of the cellular sites that regulate the mRNA half-life is the processing bodies, the dynamic cytoplasmic structures that represent the non-translating mRNA and the ribonucleoprotein complex that also control the decapping and translation of mRNA. In the present study we explored the possible role of malin E3 ubiquitin ligase in the mRNA decay pathway via the processing bodies. Defects in malin are associated with Lafora disease (LD)-a neurodegenerative disorder characterized by myoclonus seizures. We show here that malin is recruited to the processing bodies and that malin regulates the recruitment of mRNA decapping enzyme Dcp1a by promoting its degradation via the ubiquitin proteasome system. Depletion of malin results in elevated levels of Dcp1a and an altered microRNA-mediated gene silencing activity. Our study suggests that malin is one of the critical regulators of processing bodies and that defects in the mRNA processing might underlie some of the disease symptoms in LD.
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PMID:Lafora disease E3 ubiquitin ligase malin is recruited to the processing bodies and regulates the microRNA-mediated gene silencing process via the decapping enzyme Dcp1a. 2313 11