Selective enrichment of DJ-1 protein in primate striatal neuronal processes: implications for Parkinson's disease.
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.
Olzmann
James A
JA
Department of Pharmacology, Emory University, Atlanta, Georgia 30322, USA.
Bordelon
Jill R
JR
Muly
E Chris
EC
Rees
Howard D
HD
Levey
Allan I
AI
Li
Lian
L
Chin
Lih-Shen
LS
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000918:Antibody Specificity; D017124:Conserved Sequence; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D000939:Epitopes / Q000737:chemistry; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D015513:Oncogene Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D010802:Phylogeny; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D000071617:Protein Deglycase DJ-1; D051381:Rats; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure
D000939:Epitopes; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1