Familial Parkinson's disease. Alpha-synuclein and parkin.

We have reviewed recent progress in establishing the function of alpha-synuclein and parkin in relation to nigral degeneration in autosomal dominant and autosomal recessive PD. Mutations of alpha-synuclein (Ala53Thr and Ala30Pro) cause a form of autosomal dominant PD with early onset. Parkin is a novel protein expressed in the cytoplasm, including the terminal regions and Golgi apparatus. Mutations of parkin cause a form of autosomal recessive young-onset PD (ARJP). Both proteins appear to be associated with fast axonal transport. In addition, in sporadic PD, normal alpha-synuclein shows an increased tendency to self-aggregate. Thus, altered axonal transport of presynaptic proteins appears to play a crucial role in neurodegeneration in PD.