title: Characterization of fibrillation process of alpha-synuclein at the initial stage.
abstract: alpha-Synuclein is the major component of the filamentous Lewy bodies and Lewy-related neurites, neuropathological hallmarks of Parkinson's disease. Although numerous studies on alpha-synuclein fibrillation have been reported, the molecular mechanisms of aggregation and fibrillation at the initial stage are still unclear. In the present study, structural properties and propensities to form fibrils of alpha-synuclein at the initial stage were investigated using 2D (1)H-(15)N NMR spectroscopy, electron microscope, and small angle X-ray scattering (SAXS). Observation of the 2D (1)H-(15)N HSQC spectra indicated significant attenuation of many cross peak intensities in the regions of KTKEGV-type repeats and the non-Abeta component of Alzheimer's disease amyloid (NAC), suggesting that these regions contributed fibril formation. Oligomerization comprising heptamer was successfully monitored at the initial stage using the time-dependent SAXS measurements.
authors.affiliation: Department of Chemistry, College of Science and Technology, Meisei University, Hino, Tokyo 191-8506, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Tashiro
authors.forename: Masaki
authors.initials: M
authors.lastname: Kojima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kihara
authors.forename: Kouki
authors.initials: K
authors.lastname: Kasai
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kamiyoshihara
authors.forename: Kenji
authors.initials: K
authors.lastname: Uéda
authors.forename: Sakurako
authors.initials: S
authors.lastname: Shimotakahara
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D016631:Lewy Bodies / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D019906:Nuclear Magnetic Resonance, Biomolecular; D010300:Parkinson Disease / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein