科研之友
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摘要
alpha-synuclein, a member of the synuclein family, is predominately expressed in brain tissues, where it is the major component of Lewy bodies, the major hallmark of Parkinson's disease We analyzed the phylogenetics, gene structure, and effects of different forms of alpha-synuclein on in vitro protein aggregation. The synuclein phylogenetic tree showed that sequences could be classified into alpha, beta, and gamma protein groups. The orthologous gene alpha-, beta- and gamma-synuclein showed similar evolutionary distance to the paralogous gene alpha-, beta- and gamma-synuclein. Bioinformatics analysis suggests that the amino-acid sequence of human alpha-synuclein can be divided into three regions: N-terminal amphipathic region (1-60), central hydrophobic non-amyloid beta component segment (61-95), and the C-terminal acidic part (96-140). The mutant site of A30P is at the second exon of alpha-synuclein, whereas E46K is located at the third exon of alpha-synuclein. alpha-synuclein alternative splicing results in four isomers, and five exons, all of which participate in protein coding, comprising 140 amino acids to produce the major alpha-synuclein in vivo. The three alpha-synuclein isoforms are products of alternative splicing, alpha-synuclein 126,112 and 98. We also review the genetic and cellular factors that affect the aggregation of alpha-synuclein and compounds that inhibit aggregation. A better understanding of alpha-synuclein sequences, structure, and function may allow better targeted therapy and diagnosis of alpha-synuclein in Parkinson's disease and other neurodegenerative diseases
