How A Mutant Enzyme Causes Parkinson's

Mutations in the gene for the enzyme parkin can cause Parkinson's disease. Researchers know that normal parkin helps attach ubiquitin to proteins as a signal to modify or degrade the labeled proteins, but they're uncertain about parkin's physiological function. Two groups have now uncovered some answers to that question. Richard J. Youle of the National Institute of Neurological Disorders & Stroke, in Bethesda, Md., and colleagues found that normal parkin helps destroy damaged mitochondria that would otherwise trigger death of neuronal cells (J. Cell. Biol., DOI: 10.1083/jcb.200809125). Meanwhile, Michael D. Ehlers and coworkers at Duke University Medical Center report that normal parkin reduces the number and strength of excitatory synapses in neurons. Mutant parkin is less able to suppress synaptic strength and number, leading to overstimulation of neurons. The resulting neuronal damage could contribute to the disease (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0802280105).