Selective enrichment of DJ‐1 protein in primate striatal neuronal processes: Implications for Parkinson's disease

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Abstract
Mutations in DJ‐1 cause autosomal recessive, early‐onset Parkinson's disease (PD). The precise function and distribution of DJ‐1 in the central nervous system remain unclear. In this study, we performed a comprehensive analysis of DJ‐1 expression in human, monkey, and rat brains with antibodies that recognize distinct, evolutionarily conserved epitopes of DJ‐1. We found that DJ‐1 displays region‐specific neuronal and glial labeling in human and nonhuman primate brain, sharply contrasting with the primarily neuronal expression pattern observed throughout rat brain. Further immunohistochemical analysis of DJ‐1 expression in human and nonhuman primate brains showed that DJ‐1 protein is expressed in neurons within the substantia nigra pars compacta and striatum, two regions critically involved in PD pathogenesis. Moreover, immunoelectron microscopic analysis revealed a selective enrichment of DJ‐1 within primate striatal axons, presynaptic terminals, and dendritic spines with respect to the DJ‐1 expression in prefrontal cortex. Together, these findings indicate neuronal and synaptic expression of DJ‐1 in primate subcortical brain regions and suggest a physiological role for DJ‐1 in the survival and/or function of nigral‐striatal neurons. J. Comp. Neurol. 500:585–599, 2007.