Interplay of α-synuclein with Lipid Membranes: Cooperative Adsorption, Membrane Remodeling and Coaggregation

Abstract

α-Synuclein is a small neuronal protein enriched at presynaptic termini. It is hypothesized to play a role in neurotransmitter release and synaptic vesicle cycling, while the formation of α-synuclein amyloid fibrils is associated with several neurodegenerative diseases, most notably Parkinson’s Disease. The molecular mechanisms of both the physiological and pathological functions of α-synuclein remain to be fully understood, but in both cases, interactions with membranes play an important role. In this Perspective, we discuss several aspects of α-synuclein interactions with lipid membranes including cooperative adsorption, membrane remodeling and α-synuclein amyloid fibril formation in the presence of lipid membranes. We highlight the coupling between the different phenomena and their interplay in the context of physiological and pathological functions of α-synuclein.