Synuclein, dopamine and oxidative stress: co-conspirators in Parkinson's disease?

The etiology of Parkinson's disease (PD) is presently unknown. The unifying hallmark of disease is depletion of dopamine and loss of nigrostriatal dopamine neurons. Familial and sporadic forms of the disease are described. The familial mutations occur within α-synuclein and molecules involved in protein degradation and mitochondrial function. Sporadic PD is thought to involve the interplay of genetic and environmental factors. Despite disparate initiating triggers, a convergent pathobiologic model for this common neurodegenerative disease has been proposed. Likely players have emerged that may form the basis for this common pathway model of disease. In this review, we examine the role of three most implicated PD pathogenic conspirators: synuclein, dopamine and oxidative stress.