title: The remarkable conformational plasticity of alpha-synuclein: blessing or curse?
abstract: The aggregation of the protein alpha-synuclein (α-SYN) is believed to be a critical event in Parkinson's disease (PD). α-SYN is characterized by a remarkable conformational plasticity, adopting different conformations depending on the environment. In vitro, α-SYN lacks a well-defined structure. Therefore, it was classified as an 'intrinsically disordered protein'. A debate has recently begun over how α-SYN behaves in the cell: is it an intrinsically disordered protein or a stable tetramer with a low propensity for aggregation? In this review, we discuss the aggregation of α-SYN and describe factors that influence this process and their potential relevance in PD pathogenesis. We address the ways in which aggregated α-SYN mediates toxicity and might lead to PD, and propose possible therapeutic strategies.
authors: Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven, Flanders, Belgium.
authors: Angélique
authors: A
authors: Deleersnijder
authors: Melanie
authors: M
authors: Gerard
authors: Zeger
authors: Z
authors: Debyser
authors: Veerle
authors: V
authors: Baekelandt
mesh_terms: D000818:Animals; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000633:toxicity
chemical_list: D051844:alpha-Synuclein