aggregation and properties of α？synuclein and related proteins聚合和属性的α -核蛋白和相关的蛋白质.pdfVIP

Spectroscopy 15 (2001) 141–150 141 IOS Press Aggregation and properties of α-synuclein and related proteins Omar M.A. El-Agnaf a,∗ and G. Brent Irvine b a Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, UK b Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen’s University Belfast, Medical Biology Centre, Belfast BT9 7BL, UK Abstract. α-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms have been associated with early onset Parkinson’s disease. A fragment of α-synuclein has also been identified as the non-Aβ component of Alzheimer’s disease amyloid (NAC). Ageing solutions of α-synuclein and NAC leads to formation of β-sheet, detectable by circular dichroism spectroscopy, and aggregation to form amyloid-like fibrils, detectable by electron microscopy. Differences in the rates of aggregation of the fibrils formed by α-synuclein and the two mutant proteins are presented. The toxicity of α-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases. Experiments on fragments of NAC have enabled the region of NAC responsible for its aggregation and toxicity to be identi- fied. Keywords: α-Synuclein, non-Aβ-component (NAC), Parkinson’s disease, amyloid, fibrils Abbreviations: Aβ, amyloid β-peptide; NAC, non-Aβ-component of Alzheimer’s disease amyloid. 1. Introduction Synucleins are a family of small proteins (127–140 amino acid residues for the human forms) ex- pressed at highest levels in nervous tissue. Three members, α-, β-, and γ-synucleins, are the products of three genes present on three different chromosomes [10]. A fourth member, synoretin, is expressed most highly in retina [49]. The first indication of an involv