Methamphetamine binds to α-synuclein and causes a conformational change which can be detected by nanopore analysis

alpha-Synuclein is an intrinsically disordered protein of 140 amino acids which is abundant in dopaminergic neurons. Misfolding and aggregation of alpha-synuclein leads to the formation of Lewy bodies inside the neurons which is the hallmark of Parkinson's disease and related dementias. Here we show by nanopore analysis that the recreational drug, methamphetamine, binds to the N-terminus of alpha-synuclein and causes a conformational change which cannot be detected by circular dichroism spectroscopy. The results suggest a mechanism for the psychoactivity of methamphetamine as well as an increased incidence of Parkinson's disease amongst users of the drug. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.