Alpha-synuclein gene structure,evolution,and protein aggregation  

作　　者：Lili Xiong Peng Zhao Zhiyun Guo Jianhua Zhang Diqiang Li Canquan Mao 

机构地区：[1]School of Life Sciences and Bioengineering, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China [2]Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, UK [3]Institute of Forest Ecology, Environment and Protection, the Chinese Academy of Forestry, Beijing 100091, China

出　　处：《Neural Regeneration Research》2010年第18期1423-1428,共6页中国神经再生研究（英文版）

基　　金：the Fundamental Research Funds for the Central Universities,No.SWJTU09BR222,SWJTU09BR217;the Program of Southwest Jiaotong University Young Teachers Research Fund,No.2009Q057,2009Q051;the Program of the Fundamental Research Funds for the Central Universities,No.SWJTU09ZT28;the Son Program of Fundamental Platform of Science and Technology Source Condition,the Ministry of Science and Technology of China,No.2005DKA21404

摘　　要：α-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 α-synuclein on in vitro protein aggregation. The synuclein phylogenetic tree showed that sequences could be classified into α, β, and y protein groups. The orthologous gene α-, β- and y-synuclein showed similar evolutionary distance to the paralogous gene α-, β- and y-synuclein. Bioinformatics analysis suggests that the amino-acid sequence of human a-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 α-synuclein, whereas E46K is located at the third exon of α-synuclein. α-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 α-synuclein in vivo. The three α-synuclein isoforms are products of alternative splicing, α-synuclein 126, 112 and 98. We also review the genetic and cellular factors that affect the aggregation of α-synuclein and compounds that inhibit aggregation. A better understanding of α-synuclein sequences, structure, and function may allow better targeted therapy and diagnosis of α-synuclein in Parkinson＇s disease and other neurodegenerative diseases.α-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 α-synuclein on in vitro protein aggregation. The synuclein phylogenetic tree showed that sequences could be classified into α, β, and y protein groups. The orthologous gene α-, β- and y-synuclein showed similar evolutionary distance to the paralogous gene α-, β- and y-synuclein. Bioinformatics analysis suggests that the amino-acid sequence of human a-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 α-synuclein, whereas E46K is located at the third exon of α-synuclein. α-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 α-synuclein in vivo. The three α-synuclein isoforms are products of alternative splicing, α-synuclein 126, 112 and 98. We also review the genetic and cellular factors that affect the aggregation of α-synuclein and compounds that inhibit aggregation. A better understanding of α-synuclein sequences, structure, and function may allow better targeted therapy and diagnosis of α-synuclein in Parkinson＇s disease and other neurodegenerative diseases.

关 键 词：Α-SYNUCLEIN bioinformatics analysis aggregation in vitro Parkinson＇s disease neurodegenerative diseases review neural regeneration 

分 类 号：Q421[生物学—神经生物学] TS214[生物学—生理学]