title: Amino acid determinants of alpha-synuclein aggregation: putting together pieces of the puzzle.
abstract: Parkinson's disease is the second most common neurodegenerative disease, and results from loss of dopaminergic neurons in the substantia nigra. The aggregation and fibrillation of alpha-synuclein in the form of intracellular proteinaceous aggregates (Lewy bodies and Lewy neurites) have been implicated as a causative factor in this disease, as well as in several other neurodegenerative disorders, including dementia with Lewy bodies, Lewy body variant of Alzheimer's disease, multiple system atrophy and Hallervorden-Spatz disease. Thus, the aggregated forms of alpha-synuclein play a crucial role in the pathogenesis of the synucleinopathies. However, the molecular mechanisms underlying alpha-synuclein aggregation into specific filamentous inclusions remained unknown until recently. Data on the aggregation and fibrillation properties of human alpha-, beta- and gamma-synucleins, mouse alpha-synuclein and familial Parkinson's disease mutants of human alpha-synuclein (A30P and A53T) are analyzed in order to shed light on the amino acid determinants of synuclein aggregation.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz 95064, USA. uversky@hydrogen.ucsc.edu
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Fink
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D000596:Amino Acids; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein