Copper(II)-induced self-oligomerization of α-synuclein

• DOI: 10.1042/bj3400821
• Publication Date: 2015-08-10T22:06:33Z
• Authors: Seung R. PAIK; Hyun-Ju SHIN; Ju-Hyun LEE; Chung-Soon CHANG; Jongsun KIM
• Keywords: Copper toxicity; Synuclein

alpha-Synuclein is a component of the abnormal protein depositions in senile plaques and Lewy bodies Alzheimer's disease (AD) Parkinson's respectively. The was suggested to provide possible nucleation centre for plaque formation AD via selective interaction with amyloid beta/A4 (Abeta). We have shown previously that alpha-synuclein has experienced self-oligomerization when Abeta25-35 present an orientation-specific manner sequence. Here we examine this biochemically specific use various metals. Strikingly, copper(II) most effective metal ion affecting form self-oligomers presence coupling reagents such as dicyclohexylcarbodi-imide or N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. size distribution oligomers indicated monomeric oligomerized sequentially. copper-induced oligomerization be suppressed acidic C-terminus truncated by treatment endoproteinase Asp-N. In contrast, Abeta25-35-induced oligomerizations intact forms were not affected. This clearly dependent on C-terminal region its underlying biochemical mechanism distinct from oligomerization. Although physiological pathological relevance remains currently elusive, common outcome copper might useful understanding neurodegenerative disorders molecular terms. addition, homoeostasis could considered one risk factors development disease.