In Parkinson's disease patients, alpha-synuclein is the major component of the intracellular protein aggregates found in dopaminergic neurons. Previously, short synthetic alpha-synuclein-derived peptides have been shown to not only prevent alpha-synuclein fibrillation but also dissolve preformed alpha-synuclein aggregates in vitro. The hexapeptide PGVTAV was the shortest peptide that retained the ability to block alpha-synuclein fibrillation. For preventative or therapeutic effectiveness, a treatment must suppress the neurotoxicity of alpha-synuclein aggregates and remain stable in plasma. The present study shows that specific peptides can protect neuronal cells from alpha-synuclein aggregation-induced cell death. The beta-sheet-breaking hexapeptide PGVTAV remained intact in human plasma for longer than one day, suggesting that it may be a candidate for the development of therapeutics to treat Parkinson's disease. (C) 2011 Elsevier Inc. All rights reserved.