Alpha-synuclein: its biological function and role in neurodegenerative diseases

Abstract

Alpha-synuclein is regarded as a presynaptic protein, which may play an important role in neuronal plasticity. However, the actual physiological function of this protein is not completely clear. Abnormal accumulation of fibrillar alpha-synuclein in Lewy bodies, as well as mutations in the alpha-synuclein gene identified in the familial forms of Parkinson's disease, point to a central role of this protein in the pathophysiology of Lewy body-related disorders. In vivo and in vitro studies showed that overexpression of alpha-synuclein, its aggregation, and interaction with other proteins are the most critical factors affecting the survival of neurons. In Alzheimer's disease, the amount of alpha-synuclein is found to be elevated at synapses, whereas a peptide derived from alpha-synuclein is thought to represent an intrinsic component of amyloid plaques. It is likely that in this disorder alpha-synuclein plays a dual role by being involved not only in synaptic function but also in amyloid beta-fibrillogenesis.