Structures and Interactions of alpha-Synuclein.Physiological and Pathologic al Relevance.

alpha-Synuclein is an intrinsically unfolded protein, which is able to adopt a partially helical structure when it interacts with different lipid membranes. Its pathological relevance is linked to its involvement in several neurodegenerative disorders including Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies. Typical of such ailments is the presence of alpha-synuclein aggregates in a beta- structure that can be soluble or precipitate. Although the physiological function of alpha-synuclein is not yet clear, its interaction with many other proteins has been proposed. The conformation adopted by alpha-synuclein in these putative complexes is still unknown. This review focuses on the current knowledge of the various conformations adopted by alpha-synuclein in different situations. The relevance of a specific conformation for the physiological function of the protein or for its purported pathological role is described. Particular emphasis is put on the conformational changes that may occur upon interaction of alpha-synuclein with various cellular components, including membranes, other copies of alpha-synuclein, and metal ions.