A novel, high-efficiency cellular model of fibrillar alpha-synuclein inclusions and the examination of mutations that inhibit amyloid formation.

ABSTRACT: Intracytoplasmic alpha-synuclein (alpha-syn) amyloidogenic inclusions are a major pathological feature of Parkinson's disease, dementia with Lewy body disease and multiple systems atrophy. The mechanisms involved in the formation and inhibition of these aggregates are areas of intense investigation. The present study characterizes a novel cellular model for the study of alpha-syn aggregation, incorporating nucleation-dependent aggregation and a new function for calcium phosphate precipitation. Cultured cells were readily induced to develop large, cytoplasmic alpha-syn filamentous aggregates that were hyperphosphorylated, often ubiquitinated and thioflavin positive. These cellular aggregates formed in the majority of transfected cells and recruited approximately half of endogenously express

SUBMITTER: Waxman EA 

PROVIDER: S-EPMC2907888 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature