title: [Pathogenesis and treatment of stroke-like episodes in MELAS].
abstract: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a distinct clinical syndrome caused by mutations in mitochondrial DNA. Crucial molecular mechanism includes a lack of taurine modification at the wobble uridine of the mutant tRNA(Leu(UUR)), causing UUG condon-specific translational defect and mitochondrial protein synthesis failure. However, the pathogenesis of stroke-like episodes remains unknown. We previously reported that stroke-like episodes were more likely non-ischemic events, characterized by increased capillary permeability, hyperperfusion, neuronal vulnerability and neuronal hyperexcitability, in which neuronal hyperexcitability plays an important role in initiation of the cascades of stroke-like events by increasing energy demand. We also emphasized a role of prolonged epileptic activities in progressive spread of stroke-like lesions, and then proposed a non-ischemic neurovascular cellular mechanism. Once neuronal hyperexcitability developed in a localized region as a result from either mitochondrial dysfunction in capillary endothelial cells, or in neurons or astrocytes, epileptic activities depolarize adjacent neurons, leading to propagation of epileptic activities in surrounding cortex. Increased capillary permeability in the presence of mitochondrial capillary angiopathy may cause unique edematous lesions predominantly involving the cortex. As a consequence, most susceptible layers of the cortex may result in neuronal loss. Therapeutic targets include each ongoing process of the disease.
authors.affiliation: Department of Neurology, School of Medicine, Kitasato University.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iizuka
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics; D003952:Diagnostic Imaging; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009154:Mutation; D050781:Transcranial Magnetic Stimulation
chemical_list: D004272:DNA, Mitochondrial