Synucleins are a family of soluble proteins common to vertebrates, primarily expressed in neural tissue and in certain tumors. The synuclein family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein. Interest in the synuclein family began when alpha-synuclein was found to be mutated in several families with autosomal dominant Parkinson's disease. All synucleins have in common a highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins. Normal cellular functions have not been determined for any of the synuclein proteins. Some data suggest a role in the regulation of membrane stability and/or turnover. Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease and the protein aggregates abnormally in Parkinson's disease, Lewy body disease, and other neurodegenerative diseases. Beta-synuclein is suggested to be an inhibitor of alpha-synuclein aggregation, which occurs in neurodegenerative diseases such as Parkinson's disease. Thus, beta-synuclein may protect the central nervous system from the neurotoxic effects of alpha-synuclein and provide a novel treatment of neurodegenerative disorders.
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