Structural insights on physiological functions and pathological effects of α-synuclein

alpha-Synuclein is an intrinsically unfolded protein that can 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. This review focuses on the structural knowledge acquired in recent years on the various conformations accessible to alpha-synuclein and to its pathologically relevant mutants. Furthermore, the role of the different variables of the chemical environments that govern the equilibria among the accessible conformations is also reviewed. The hypotheses that rationalize the relevance of the individual structural features and conformations for the physiological function of the protein or for its purported pathological role are described and compared. - Bisaglia, M., Mammi, S., Bubacco, L. Structural insights on physiological functions and pathological effects of alpha-synuclein. FASEB J. 23, 329-340 (2009)