beta-Sheet-breaking peptides inhibit the fibrillation of human alpha-synuclein.
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.
Kim
You Soon
YS
Department of Molecular Biology, Sejong University, Seoul, Republic of Korea.
Lim
Dongyeol
D
Kim
Joo Yeon
JY
Kang
Shin Jung
SJ
Kim
Yang-Hee
YH
Im
Hana
H
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*
D000978:Antiparkinson Agents; D009842:Oligopeptides; D051844:alpha-Synuclein