Alpha-synuclein and neurodegenerative diseases

In recent years, two developments have imparted a new direction to research on the aetiology and pathogenesis of Parkinson's disease. First, the discovery that a missense mutation in the alpha -synuclein gene is a rare genetic cause of Parkinson's disease. Second, the identification of the alpha -synuclein protein as the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of all cases of Parkinson's and several other diseases. The filamentous inclusions of multiple system atrophy are also made of alpha -synuclein. These findings have placed alpha -synuclein dysfunction at the centre of several common neurodegenerative diseases. Here, I review the molecular properties of the synucleins, the different diseases characterized by the accumulation of a-synuclein, and the possible mechanisms by which dysfunction of a-synuclein might lead to neurodegeneration.