Provoking thoughts on Parkinson’s disease

Mutations in the Pink1 and Parkin genes are associated with early-onset Parkinson’s disease (PD)—a neurodegenerative disorder with motor symptoms due to loss of dopaminergic neurons. PINK1 and Parkin have been shown to repress mitochondrial antigen presentation, suggesting that mutations in Pink1 and Parkin may unleash autoimmunity. Michel Desjardins and colleagues show that in mice without Pink1, not the normal variety, a Gram-negative bacterial infection in the intestine indeed results in mitochondrial antigen presentation and the generation of mitochondria specific CD8⁺ T cells that patrol the periphery and the brain. Remarkably, the infected mice develop motor impairments, which are transient and reversible by L-DOPA and coincide with a decreased density of dopaminergic axonal varicosities. These findings suggest that PINK1 is a repressor of autoimmunity, and provide a new way to think about PD.