Missense mutations (A30P and A53T) in alpha-synuclein and the overproduction of the wild-type protein cause familial forms of Parkinson's disease and dementia with Lewy bodies.
Later, the discovery of two missense mutations (G88C and G209A), which resulted in Ala30Pro (A30P) and Ala53Thr (A53T) substitutions, of the alpha-synuclein gene in certain autosomal-dominant early onset familial Parkinson's disease (PD) has greatly promoted the understanding of the role of alpha-synuclein in the pathogenesis of neurodegenerative diseases, such as PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) [5,6,51,75].
The presynaptic protein alpha-synuclein is a prime suspect for contributing to Lewy pathology and clinical aspects of diseases, including Parkinson's disease, dementia with Lewy bodies, and a Lewy body variant of Alzheimer's disease. alpha-Synuclein accumulates in Lewy bodies and Lewy neurites, and two missense mutations (A53T and A30P) in the alpha-synuclein gene are genetically linked to rare familial forms of Parkinson's disease.