Alpha-synuclein: its biological function and role in neurodegenerative diseases.
Alpha-synuclein is regarded as a presynaptic protein, which may play an important role in neuronal plasticity. However, the actual physiological function of this protein is not completely clear. Abnormal accumulation of fibrillar alpha-synuclein in Lewy bodies, as well as mutations in the alpha-synuclein gene identified in the familial forms of Parkinson's disease, point to a central role of this protein in the pathophysiology of Lewy body-related disorders. In vivo and in vitro studies showed that overexpression of alpha-synuclein, its aggregation, and interaction with other proteins are the most critical factors affecting the survival of neurons. In Alzheimer's disease, the amount of alpha-synuclein is found to be elevated at synapses, whereas a peptide derived from alpha-synuclein is thought to represent an intrinsic component of amyloid plaques. It is likely that in this disorder alpha-synuclein plays a dual role by being involved not only in synaptic function but also in amyloid beta-fibrillogenesis.
Kaplan
Batia
B
Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer 52621, Israel. kaplanb@sheba.health.gov.il
Ratner
Vladimir
V
Haas
Elisha
E
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D016631:Lewy Bodies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000473:pathology; D051843:Synucleins; D051844:alpha-Synuclein
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein