Interaction of alpha-synuclein with lipids

Alpha-synuclein (α-syn) is a natively unfolded protein that is abundantly expressed in the central nervous system. Although it has been shown to be involved in neurotransmission and cognition, its exact functions remain elusive. The misfolding of this protein into β-sheet-rich amyloid structures and subsequent aggregation has been associated with several neurodegenerative diseases, including Parkinson's disease. The interaction of α-syn with lipid membranes has been implicated in the formation of these pathological aggregates. At the same time, some physiological functions of α-syn also seem to require membrane interactions. A majority of the disease-associated mutations of α-syn occur in the lipid binding domain, further indicating the importance of membrane interactions in health and disease. A comprehensive understanding of the factors that modulate these interactions will help delineate the physiological and pathological states of this protein.