title: beta-Sheet-breaking peptides inhibit the fibrillation of human alpha-synuclein.
abstract: alpha-Synuclein is the major components of the intracellular protein-aggregates, found in the dopaminergic neurons of Parkinson's disease patients. Previously, we screened for alpha-synuclein substitution mutants that prevent fibril formation of both wild-type and Parkinson's disease-linked alpha-synuclein variants. In the present study, we show that short synthetic peptides derived from these mutant sequences not only prevented alpha-synuclein fibrillation but also dissolved preformed alpha-synuclein aggregates in vitro. The hexapeptide PGVTAV, which was the shortest peptide that retained the ability to block alpha-synuclein fibrillation, may serve as a lead compound for the development of therapeutics for Parkinson's disease.
authors.affiliation: Department of Molecular Biology, Sejong University, Seoul, Republic of Korea.
authors.forename: You Soon
authors.initials: YS
authors.lastname: Kim
authors.forename: Dongyeol
authors.initials: D
authors.lastname: Lim
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Shin Jung
authors.initials: SJ
authors.lastname: Kang
authors.forename: Yang-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Hana
authors.initials: H
authors.lastname: Im
mesh_terms: D000595:Amino Acid Sequence; D000978:Antiparkinson Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D009842:Oligopeptides; D051844:alpha-Synuclein