Effect of ParkinsonвЂ™s disease-linked mutations. Membrane association and protein conformation of О±-synuclein in intact neurons. Aggregates assembled from overexpression of wild-type О±-synuclein are not toxic to human neuronal cells. О±-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. Determination of the secondary structures of proteins by circular dichroism and optical rotatory dispersion. Mechanistic aspects of ParkinsonвЂ™s disease: О±-synuclein and the biomembrane. Mass mapping of large globin complexes by scanning transmission electron microscopy. Cryoelectron microscopy structure of purified Advantages and limitations of clear-native PAGE. GATA transcription factors directly regulate the ParkinsonвЂ™s disease-linked gene О±-synuclein. Missense tau mutations identified in FTDP-17 have a small effect on tau-microtubule interactions. Stabilization of О±-synuclein secondary structure upon binding to synthetic membranes. NACP, a protein implicated in AlzheimerвЂ™s disease and learning, is natively unfolded. Brain О±-synuclein accumulation in multiple system atrophy, ParkinsonвЂ™s disease and progressive supranuclear palsy: a comparative investigation. The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. What causes cell death in ParkinsonвЂ™s disease? Ann. Missing pieces in the ParkinsonвЂ™s disease puzzle. On the basis of these findings, we propose that destabilization of the helically folded tetramer precedes О±-synuclein misfolding and aggregation in ParkinsonвЂ™s disease and other human synucleinopathies, and that small molecules that stabilize the physiological tetramer could reduce О±-synuclein pathogenicity. Whereas recombinantly expressed monomers readily aggregated into amyloid-like fibrils in vitro, native human tetramers underwent little or no amyloid-like aggregation. Native, cell-derived О±-synuclein showed О±-helical structure without lipid addition and had much greater lipid-binding capacity than the recombinant О±-synuclein studied heretofore. Several methods, including analytical ultracentrifugation, scanning transmission electron microscopy and in vitro cell crosslinking confirmed the occurrence of the tetramer. In contrast, we report that endogenous О±-synuclein isolated and analysed under non-denaturing conditions from neuronal and non-neuronal cell lines, brain tissue and living human cells occurs in large part as a folded tetramer of about 58вЂ‰kDa. This concept derives from the widespread use of recombinant bacterial expression protocols for in vitro studies, and of overexpression, sample heating and/or denaturing gels for cell culture and tissue studies. 6) that is believed to acquire О±-helical secondary structure only upon binding to lipid vesicles 7. О±-Synuclein has long been defined as a вЂnatively unfoldedвЂ™ monomer of about 14вЂ‰kDa (ref. Intraneuronal aggregates of О±-synuclein occur in Lewy bodies and Lewy neurites 5, the cytopathological hallmarks of ParkinsonвЂ™s disease and related disorders called synucleinopathies 4. Growing evidence indicates a causative role of misfolded forms of the protein О±-synuclein in the pathogenesis of ParkinsonвЂ™s disease 3, 4. ParkinsonвЂ™s disease is the second most common neurodegenerative disorder 1, 2.

Biorad gel filtration standard 151 1901