title: Membrane interactions of oligomeric alpha-synuclein: potential role in Parkinson's disease.
abstract: alpha-Synuclein is a small neuronal protein that has been implicated to play an important role in Parkinson's disease. Genetic mutations and multiplications in the alpha-synuclein gene can cause familial forms of the disease. In aggregated fibrillar form, alpha-synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinson's disease. The loss of functional dopaminergic neurons in Parkinson's disease may be caused by a gain in toxic function of the protein. Elucidating if this gain of toxic function is related to the aggregation of alpha-synuclein may be vital in understanding Parkinson's disease. Although there are many ideas on how alpha-synuclein could be involved in the disease, this review will focus on the amyloid pore hypothesis. This hypothesis assumes that aggregation intermediates or oligomers are more likely to be toxic than monomeric or fibrillar forms of the protein. Oligomeric species are thought to exercise their toxicity through permeabilization of cellular membranes. Membrane pore formation by an oligomeric intermediate might play a role in other neurodegenerative disorders in which protein aggregation and amyloid formation play a role, such as Alzheimer's disease. We will discuss the role of this hypothesis in Parkinson's disease.
authors.affiliation: MESA+ Institute for Nanotechnology & MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Bart D
authors.initials: BD
authors.lastname: van Rooijen
authors.forename: Mireille M A E
authors.initials: MM
authors.lastname: Claessens
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity
chemical_list: D051844:alpha-Synuclein