Parkinson's disease (PD) is one of the most common neurodegenerative disorders characterized by the progressive loss of dopaminergic neurons in the substatia nigra. Following the loss of dopaminergic neurons is the accumulation of the inclusion bodies commonly referred to as Lewy bodies that contain α-synuclein, synphilin, SIAH and parkin. These are small proteins that have special relevance for understanding PD. Not only are α-synuclein, synphilin, SIAH and parkin found in Lewy bodies characteristic of PD, but also mutations in the gene for α- synuclein, synphilin, SIAH or parkin can cause an inherited form of PD and over-expression of normal α-synuclein or synphilin is thought to increase the risk of developing PD in sporadic or non-familial cases. However, the mechanisms involved in the death of dopaminergic neurons as well as the role of Lewy bodies in the pathogenesis of the PD are still unclear. Parkin and SIAH are E3 ubiquitin-ligases that ubiquitylate themselves and promote their own degradation. Parkin and SIAH interact with polyubiquitylate synphilin (the α-synuclein interacting protein) and in the same manner monoubiquitylate α-synuclein. Taken together, formation of Lewy bodies occurs upon coexpression of α-synuclein, synphilin, SIAH and parkin. This review discusses the way and manner in which the interaction of α-synuclein, synphilin, SIAH and parkin has been thought to be responsible for developing PD
