Prion-like behaviour of α-synuclein

[Speaker] Hiroyuki Oshikane:1
[Co-author] Masahiko Watabe:1,2, Naoya Tochio:3, Fumio Arisaka:4, Naoko Tate:3, Toshio Nakaki:1
1:Department of Pharmacology, Teikyo University School of Medicine, Japan, 2:General Medical Education and Research Center (G-MEC), Teikyo University, Japan, 3:Laboratory of Basic Chemistry and Molecular Structure, Faculty of Pharma Sciences, Teikyo University, Japan, 4:Tokyo Institute of Technology, Japan

 α-synuclein is known to form irreversible aggregation called Lewy body in the patients suffering from neurodegenerative diseases including Parkinson's disease (PD). α-synuclein --a non-essential protein which possibly assists the neuronal Golgi apparatus function and vesicle trafficking-- is considered to be intrinsically disordered protein (IDP), lacking specific three dimensional structure. Stoichiometry of α-synuclein protein can change from monomer, oligomer to fibrillar form (toxic form), the molecular mechanism for which has been extensively studied to date. Recently, α-synuclein is suggested to be a prion-like molecule capable of both infection and propagation, perhaps thereby impairing the cellular metabolism and signalling of other individuals. In order to assess the prion-like behaviour of α-synuclein, we employed comprehensive biophysical, biochemical and cell biological means including chromatographic analysis, circular dichroism (CD) spectroscopic analysis, thioflavin T (ThT) assay, crosslinking assay, ultra centrifugal analysis, Fluorescence resonance energy transfer (FRET) analysis and bio-imaging technique. Here, we present preliminary experimental data of α-synuclein as prion-like molecule through these studies, providing insights into the molecular mechanism of pathogenesis of neurodegenerative diseases.

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