Department of Psychiatry and Neurosciences, Neuroimmunology Laboratory, University of South Florida, College of Medicine, Tampa, FL 33613, USA.
Mol Neurodegener. 2011 Jan 11;6(1):3. doi: 10.1186/1750-1326-6-3.
Microglial dysfunction is associated with the pathogenesis and progression of a number of neurodegenerative disorders including HIV associated dementia (HAD). HIV promotion of an M1 antigen presenting cell (APC) - like microglial phenotype, through the promotion of CD40 activity, may impair endogenous mechanisms important for amyloid- beta (Aβ) protein clearance. Further, a chronic pro-inflammatory cycle is established in this manner. CD45 is a protein tyrosine phosphatase receptor which negatively regulates CD40L-CD40-induced microglial M1 activation; an effect leading to the promotion of an M2 phenotype better suited to phagocytose and clear Aβ. Moreover, this CD45 mediated activation state appears to dampen harmful cytokine production. As such, this property of microglial CD45 as a regulatory "off switch" for a CD40-promoted M1, APC-type microglia activation phenotype may represent a critical therapeutic target for the prevention and treatment of neurodegeneration, as well as microglial dysfunction, found in patients with HAD.
小胶质细胞功能障碍与许多神经退行性疾病的发病机制和进展有关，包括 HIV 相关痴呆（HAD）。HIV 通过促进 CD40 活性，促进一种类似于 M1 抗原呈递细胞（APC）的小胶质细胞表型，可能会损害内源性清除淀粉样蛋白-β（Aβ）蛋白的重要机制。此外，以这种方式建立了慢性促炎循环。CD45 是一种蛋白酪氨酸磷酸酶受体，可负调控 CD40L-CD40 诱导的小胶质细胞 M1 激活；这种作用导致促进更适合吞噬和清除 Aβ 的 M2 表型。此外，这种 CD45 介导的激活状态似乎抑制了有害细胞因子的产生。因此，小胶质细胞 CD45 作为 CD40 促进的 M1、APC 样小胶质细胞激活表型的调节“关闭开关”的特性，可能代表预防和治疗 HAD 患者神经退行性变和小胶质细胞功能障碍的关键治疗靶点。
