Koistinaho Milla, Koistinaho Jari
Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.
Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
Glia. 2002 Nov;40(2):175-183. doi: 10.1002/glia.10151.
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.
尽管小胶质细胞被认为在中枢神经系统（CNS）的再生和可塑性中发挥有益作用，但最近的研究表明，小胶质细胞释放的至少某些分子在急性脑损伤和神经退行性疾病中可能是有害的。因此，介导这些神经毒性化合物合成和释放的途径至关重要。小胶质细胞中的丝裂原活化蛋白激酶（MAPK）的p38和p44/42家族对各种细胞外刺激有强烈反应，如ATP、凝血酶和β-淀粉样蛋白，一种被认为与阿尔茨海默病神经病理学有关的肽。在这篇综述中，我们描述了体内证据，表明p38和p44/42 MAPK可能在急性脑损伤（如中风）以及更慢性的神经退行性疾病（如阿尔茨海默病）中有害的小胶质细胞激活中起关键作用。我们还阐明了负责激活小胶质细胞中p38和p44/42 MAPK的细胞外信号，并综述了迄今为止报道的由这些激酶介导的反应。
