title: Methamphetamine binds to α-synuclein and causes a conformational change which can be detected by nanopore analysis.
abstract: α-Synuclein is an intrinsically disordered protein of 140 amino acids which is abundant in dopaminergic neurons. Misfolding and aggregation of α-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 α-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.
authors: Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada.
authors: Omid
authors: O
authors: Tavassoly
authors: Jeremy S
authors: JS
authors: Lee
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016631:Lewy Bodies / Q000187:drug effects / Q000378:metabolism; D020961:Lewy Body Disease / Q000209:etiology / Q000378:metabolism; D008694:Methamphetamine / Q000378:metabolism* / Q000633:toxicity; D008958:Models, Molecular; D058608:Nanopores; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D008694:Methamphetamine