A novel role for parkin in trauma-induced central nervous system secondary injury

Recently, loss-of-function mutations of parkin have been identified as being causally related to autosomal recessive juvenile parkinsonism, the most common form of familial Parkinson’s disease. In addition to functioning as an E3 ubiquitin ligase that facilitates the proteasomal degradation of proteins with abnormal conformations, parkin protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. Parkin is expressed throughout the brain in a variety of functional and neurochemical systems. We propose that parkin’s role in protecting neurons from oxidative stress may extend beyond the nigrostriatal system to include neurons in other regions of the central nervous system. This is relevant for therapeutic strategies for brain and spinal cord injury because oxidative stress leading to lipid peroxidation and protein and nucleic acid oxidation is a significant cause of secondary injury and thus neuronal death following traumatic injuries to the central nervous system. A novel model system to verify the process of oxidative stress as a causative factor in trauma-induced secondary injury mechanisms would be to induce traumatic brain and spinal cord injury in parkin-null mice. This is expected to provide the proof-of-principle that a cascade of oxidative stress is a causal event leading to secondary neuronal injury, that parkin functions outside of the dopaminergic system to protect other neurons from oxidative stress, and that antioxidant pharmacotherapy is a rational therapeutic approach to decrease trauma-induced neuronal injury.