Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions

Parkinson disease (PD) is a neurodegenerative disease characterized by tremor, bradykinesia, rigidity and postural instability. Post-mortem examination shows loss of neurons and Lewy bodies, which are cytoplasmic eosinophilic inclusions, in the substantia nigra and other brain regions 1 , 2 . A few families have PD caused by mutations (A53T or A30P) in the gene SNCA (encoding α-synuclein; refs 3 , 4 , 5 ). α-synuclein is present in Lewy bodies of patients with sporadic PD (Refs 6 , 7 ), suggesting that α-synuclein may be involved in the pathogenesis of PD. It is unknown how α-synuclein contributes to the cellular and biochemical mechanisms of PD, and its normal functions and biochemical properties are poorly understood 8 , 9 , 10 . To determine the protein-interaction partners of α-synuclein, we performed a yeast two-hybrid screen. We identified a novel interacting protein, which we term synphilin-1 (encoded by the gene SNCAIP ). We found that α-synuclein interacts in vivo with synphilin-1 in neurons. Co-transfection of both proteins (but not control proteins) in HEK 293 cells yields cytoplasmic eosinophilic inclusions.