Microglia in neurodegeneration: molecular aspects.
Inflammatory events in the CNS are associated with injuries as well as with well-known chronic degenerative diseases, such as Multiple Sclerosis, Parkinson's, or Alzheimer's disease. Compared to inflammation in peripheral tissues, inflammation in brain appears to follow distinct pathways and time-courses, which likely has to do with a relatively strong immunosuppression in that organ. For this reason, it is of great importance to get insights into the molecular mechanism governing immune reactions in brain tissue. This task is hard to achieve in vivo, but can be approached by studying the major cell type responsible for brain inflammation, the microglia, in culture. Since these cells are the only professional antigen-presenting cells resident in brain parenchyma, molecular mechanisms of antigen presentation are being discussed first. After covering the expression and regulation of anti- and proinflammatory cytokines, induction and regulation of two key enzymes and their products-COX-2 and iNOS-are summarized. Possibly, pivotal molecular targets for drug therapies of brain disorders will be discovered in intracellular signaling pathways leading to activation of transcription factors. Finally, the impact of growth factors, of neurotrophins in particular, is highlighted. It is concluded that the presently available data on the molecular level is far from being statisfying, but that only from better insights into molecular events will we obtain the information required for more specific therapies.
Gebicke-Haerter
P J
PJ
Department of Psychopharmacology, Central Institute for Mental Health, Mannheim, Germany. gebicke@as200.zi-mannheim.de
D000818:Animals; D017951:Antigen Presentation; D001921:Brain / Q000276:immunology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D017628:Microglia / Q000276:immunology / Q000502:physiology*; D009410:Nerve Degeneration / Q000276:immunology / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000502:physiology; D009422:Nervous System Diseases / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D014157:Transcription Factors; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium