The hexapeptide PGVTAV suppresses neurotoxicity of human α-synuclein aggregates

In Parkinson’s disease patients, α-synuclein is the major component of the intracellular protein aggregates found in dopaminergic neurons. Previously, short synthetic α-synuclein-derived peptides have been shown to not only prevent α-synuclein fibrillation but also dissolve preformed α-synuclein aggregates in vitro. The hexapeptide PGVTAV was the shortest peptide that retained the ability to block α-synuclein fibrillation. For preventative or therapeutic effectiveness, a treatment must suppress the neurotoxicity of α-synuclein aggregates and remain stable in plasma. The present study shows that specific peptides can protect neuronal cells from α-synuclein aggregation-induced cell death. The β-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.

► The hexapeptide PGVTAV was shown previously to block α-synuclein fibrillation. ► We show here the peptide prevented conversion of α-synuclein monomers into oligomers. ► The peptide protected neuronal cells from α-synuclein aggregation-induced cell death. ► The hexapeptide was resistant to plasma proteases and remained intact in human plasma.