Synucleins and their relationship to Parkinson's disease

Parkinson's disease (PD) is one of the most common neurodegenerative motor disorders, marked by chronic progressive loss of neurons in the substantia nigra. It has long been believed that PD is caused by environmental factors. The discovery of genetic factors involved in PD has improved the understanding of the pathology of the disease. The first gene found to be mutated in PD encodes for the presynaptic protein alpha-synuclein. alpha-Synuclein is a major component of Lewy bodies and Lewy neurites, which represent the morphological hallmarks of the disease. The mechanisms by which alpha-synuclein is involved in nigral cell death remain poorly understood. Moreover, the factors triggering the formation of alpha-synuclein-positive inclusion bodies remain enigmatic. Indeed, even the normal cellular functions of alpha-synuclein and of the other synucleins (beta-synuclein and gamma-synuclein) are still unknown. Several lines of evidence suggest that they play a role in the regulation of vesicular turnover under normal nonpathological conditions.