The many faces of alpha-synuclein: from structure and toxicity to therapeutic target

Disorders characterized by alpha-synuclein (alpha-syn) accumulation, Lewy body formation and parkinsonism (and in some cases dementia) are collectively known as Lewy body diseases. The molecular mechanism (or mechanisms) through which a-syn abnormally accumulates and contributes to neurodegeneration in these disorders remains unknown. Here, we provide an overview of current knowledge and prevailing hypotheses regarding the conformational, oligomerization and aggregation states of alpha-syn and their role in regulating alpha-syn function in health and disease. Understanding the nature of the various alpha-syn structures, how they are formed and their relative contributions to alpha-syn-mediated toxicity may inform future studies aiming to develop therapeutic prevention and intervention.