Aging and neurodegeneration. Molecular mechanisms of neuronal loss in Huntington's disease.
Huntington's disease (HD) is a fatal, genetically based late-onset neurodegenerative disorder in which a loss of neostriatal neurons is a main characteristic. The CAG trinucleotide repeat expansion encoding polyglutamine tract induces progressive deficits in intra- and inter-cellular signalling, and subsequent clinical signs developed with aging process. CAG-induced neurodegeneration and disease-onset shows aging-dependent pattern. Proposed mechanism of neurodegeneration includes intranuclear or intracellular protein aggregates, proteolytic cleavage of huntingtin (cf. caspase, calpain), altered transcription or other neurotransmitter signalling deficits. Recently, stem cell transplantation is of benefit to protect neurons against neurodegeneration and recover the functional deficit in the experimental HD model. This review focuses on current knowledge of molecular mechanisms in neurodegeneration and potential therapeutic targets in HD.
Lee
Soon-Tae
ST
Department of Neurology, Seoul National University Hospital, Chongnoku, Republic of Korea.
Kim
Manho
M
D000375:Aging; D000818:Animals; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology*; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020169:Caspases