Inflammatory process in Parkinson's disease: role for cytokines.
Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and decreased levels of neurotrophins such as brain-derived neurotrophic factor (BDNF) in the nigrostriatal region of postmortem brains and/or in the ventricular or lumbar cerebrospinal fluid (CSF) from patients with sporadic PD, and in animal models, such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)- and 6-hydroxydopamine (6-OHDA)-induced PD. These changes in cytokine and neurotrophin levels may be initiated by activated microglia, which may then promote apoptotic cell death and subsequent phagocytosis of DA neurons. Cytokines as pleiotropic factors, promote signals that either lead to cell death or exert neuroprotective effects. The discovery of toxic changes in trophic microglia by M. Sawada and co-workers is important to this point. Ultimately, microglial cells may regulate cellular changes that cause either harm or benefit by producing cytokines or neurotrophins depending upon the primary cause and the circumstances during the inflammatory process of PD.
Nagatsu
T
T
Fujita Health University, Institute for Comprehensive Medical Science, Toyoake, Aichi, 470-1192, Japan. tnagatsu@fujita-hu.ac.jp
Sawada
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016207:Cytokines / Q000134:cerebrospinal fluid / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D006801:Humans; D007109:Immunity / Q000502:physiology; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000473:pathology*; D017072:Neostriatum / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000502:physiology; D009457:Neuroglia / Q000502:physiology; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D013378:Substantia Nigra / Q000503:physiopathology
D016207:Cytokines; D009414:Nerve Growth Factors; D004298:Dopamine