Mitochondrial injury: a hot spot for parkinsonism and Parkinson's disease?

The recent identification of genes (parkin, DJ-1, and PINK1) involved in recessive autosomal parkinsonism, and the indications that these proteins may have protective effects on the mitochondria, has led to the reemergence of the notion that mitochondrial dysfunction might play a central role in the etiology of sporadic Parkinson's disease (PD). This idea has previously been supported by biochemical analyses showing reduced mitochondrial activity in PD patients and in animal models of PD generated by the selective inhibition of mitochondria activity. However, the involvement of DJ-1 or PINK1 loss of function in classical idiopathic PD, characterized by pathological inclusions composed of aggregated alpha-synuclein protein, has still not been evaluated. More detailed studies of the possible interactions between parkin, DJ-1, PINK1, and alpha-synuclein and their effects on mitochondria are needed to more adequately define the biological pathways that may convergently or independently lead to parkinsonism.