Role of p38 and p44/42 mitogen-activated protein kinases in microglia.
Although microglial cells are thought to play a beneficial role in the regeneration and plasticity of the central nervous system (CNS), recent studies have indicated that at least some molecules released by microglia may be harmful in acute brain insults and neurodegenerative diseases. Therefore, the pathways mediating the synthesis and release of these neurotoxic compounds are of importance. p38 and p44/42 families of mitogen-activated protein kinases (MAPKs) in microglia respond strongly to various extracellular stimuli, such as ATP, thrombin, and beta-amyloid, a peptide thought to be responsible for the neuropathology in Alzheimer's disease. In this review we describe in vivo evidence implicating that p38 and p44/42 MAPKs may play a critical role in harmful microglial activation in acute brain injury, such as stroke, and in more chronic neurodegenerative diseases, such as Alzheimer's disease. We also clarify the extracellular signals responsible for activation of p38 and p44/42 MAPK in microglia and review the responses so far reported to be mediated by these kinases.
Koistinaho
Milla
M
Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.
Koistinaho
Jari
J
Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.|Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
D000818:Animals; D001930:Brain Injuries / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000201:enzymology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000201:enzymology; D020521:Stroke / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases
D008070:Lipopolysaccharides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases