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Clues to how alpha-synuclein damages neurons in Parkinson's disease

✍ Scribed by David Sulzer

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
68 KB
Volume
25
Category
Article
ISSN
0885-3185

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✦ Synopsis

Abstract

Alpha‐synuclein (α‐syn) appears to normally regulate neurotransmitter release, possibly via calcium‐dependent binding and dissociation from lipid domains on secretory vesicles. The pathogenic effects of α‐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 α‐syn, pathogenic mutations of α‐syn, and dopamine‐modified‐α‐syn promote toxic interaction between α‐syn oligomers and lipids. These may disrupt transmembrane concentration gradients across secretory vesicles and other organelles and interfere with normal lysosomal or ubiqutin/proteasome mediated protein degradation or mitochondrial function. Additional causes of PD may interfere at other points with normal handling and degradation of α‐syn, providing a variety of entry points to a converging neurodegenerative path underlying the disease. © 2010 Movement Disorder Society

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