期刊
MOVEMENT DISORDERS
卷 25, 期 3, 页码 S27-S31出版社
WILEY
DOI: 10.1002/mds.22639
关键词
alpha-synuclein; Parkinson's disease
资金
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P50NS038370] Funding Source: NIH RePORTER
- NINDS NIH HHS [P50 NS038370] Funding Source: Medline
Alpha-synuclein (alpha-syn) appears to normally regulate neurotransmitter release, possibly via calcium-dependent binding and dissociation from lipid domains on secretory vesicles. The pathogenic effects of alpha-syn leading to Parkinson's disease (PD) appear to result from alternate toxic effects on lipid membrane. A variety of findings indicate that overexpression of wild-type alpha-syn, pathogenic mutations of alpha-syn. and dopamine-modified-alpha-syn promote toxic interaction between alpha-syn oligomers and lipids. These may disrupt transmembrane concentration gradients across secretory vesicles and other organelles and interfere with normal lysosomal or ubigutin/proteasome mediated protein degradation or mitochondrial function. Additional causes of PD may interfere at other points with normal handling and degradation of alpha-syn, providing a variety of entry points to a converging neurodegenerative path underlying the disease. (C) 2010 Movement Disorder Society
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