p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the parkinsonian brain.
We and other workers found markedly increased levels of proinflammatory cytokines and apoptosis-related proteins in parkinsonian brain. Although the pathogenesis of Parkinson's disease (PD) remains enigmatic, apoptosis might be involved in the degeneration of dopaminergic neurons in PD. To investigate the possible presence of other inflammatory cytokines and/or apoptosis-related protein, the levels of p53 protein, interferon-gamma, and NF-kappaB were measured for the first time in the brain (substantia nigra, caudate nucleus, putamen, cerebellum, and frontal cortex) from control and parkinsonian patients by a highly sensitive sandwich enzyme-linked immunosorbent assay. The p53 protein level in the caudate nucleus was significantly higher in parkinsonian patients than in controls (P<0.05), whereas this protein in the substantia nigra, putamen, and cerebral cortex showed no significant difference between parkinsonian and control subjects. The interferon-gamma level was significantly higher in the nigrostriatal dopaminergic regions (substantia nigra, caudate nucleus, and putamen) in parkinsonian patients than in the controls (P<0.05), but was not significantly different in the cerebellum or frontal cortex between the two groups. In accordance with previous immunohistochemical analysis, the NF-kappaB level in the nigrostriatal dopaminergic regions was significantly higher in parkinsonian patients than in the controls (P<0.05). These data suggest that the significant increase in the levels of p53 protein, interferon-gamma, and NF-kappaB reflect apoptosis and the inflammatory state in the parkinsonian brain and that their elevation is involved in the degeneration of the nigrostriatal dopaminergic neurons.
Mogi
Makio
M
Department of Medicinal Biochemistry, School of Pharmacy, Aichi-Gakuin University, Nagoya 464-8650, Japan. makio@dpc.aichi-gakuin.ac.jp
Kondo
Tomoyoshi
T
Mizuno
Yoshikuni
Y
Nagatsu
Toshiharu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009410:Nerve Degeneration / Q000276:immunology / Q000378:metabolism; D009434:Neural Pathways / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D013378:Substantia Nigra / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
D015415:Biomarkers; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma; D004298:Dopamine