An inflammatory review of Parkinson's disease.
The symptoms of Parkinson's disease (PD) were first described nearly two centuries ago and its characteristic pathology identified nearly a century ago, yet its pathogenesis is still poorly understood. Parkinson's disease is the most prevalent neurodegenerative movement disorder and research into its pathogenesis recently accelerated following the identification of a number of causal genetic mutations. The mutant gene products all cause dysfunction of the ubiquitin-proteosome system, identifying protein modification and degradation as critical for pathogenesis. Modified non-degraded intracellular proteins accumulate in certain neuronal populations in all forms of the disease. However, neuronal degeneration is more highly selective and associates with substantial activation of microglia, the inflammatory cells of the brain. We review the current change in thinking regarding the role of microglia in the brain in the context of Parkinson's disease and animal models of the disease. Comparison of the cellular tissue changes across a number of animal models using diverse stimuli to mimic Parkinson's disease reveals a consistent pattern implicating microglia as the effector for the selective degeneration of dopaminergic neurons. While previous reviews have concentrated on the intracellular neuronal changes in Parkinson's disease, we highlight the cell to cell interactions and immune regulation critical for neuronal homeostasis and survival in Parkinson's disease.
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Prince of Wales Medical Research Institute and the University of New South Wales, Sydney 2031, Royal North Shore Hospital, Sydney 2065, Australia.
Rowe
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Halliday
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000276:immunology; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015166:Monitoring, Immunologic; D009474:Neurons / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000276:immunology; D010300:Parkinson Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012402:Rotenone / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D005732:Gangliosides; D008070:Lipopolysaccharides; C082161:lipopolysaccharide A; D012402:Rotenone; C016481:trisialoganglioside GT1; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine