TREM2介导小胶质细胞吞噬功能在神经退行性疾病中的作用

Role of TREM2-mediated microglial phagocytosis in neurodegenerative diseases

以阿尔茨海默病(AD)为代表的多种慢性神经退行性疾病发病机制尚未明确。近年研究发现神经退行性疾病发生与错误折叠的蛋白质、淀粉样蛋白(Aβ)、死亡神经元和受损髓鞘吞噬清除障碍有关,而完整的小胶质细胞吞噬功能是维持中枢神经系统稳态的重要原因。小胶质细胞表面吞噬受体髓样细胞触发受体2(TREM2)表达改变可调节小胶质细胞吞噬效率,负性调节TLR诱导的炎症反应,促进M2小胶质细胞表型表达,发挥神经保护作用。此外,TREM2功能突变对小胶质细胞吞噬功能的影响与AD、帕金森病等神经退行性疾病风险增加相关。因此,了解TREM2介导的小胶质细胞吞噬清除功能在不同神经退行性疾病中的作用对于探索神经退行性疾病新的治疗方向具有重要意义。

Pathogenesis of many chronic neurodegenerative diseases represented by Alzheimer's disease(AD)is not yet clear.In recent years,numerous studies have found that occurrence of neurodegenerative diseases is related to damaged phagocytic clearance of misfolded proteins,β-amyloid protein(Aβ),dead neurons and impaired myelin,while intact phagocytic function of microglia is an important reason for maintaining homeostasis of central nervous system.Changes in expression of phagocytic receptor TREM2 on surface of microglia can regulate phagocytic efficiency of microglia,negatively regulate TLR-induced inflammatory response,promote expression of M2 microglia phenotype,and play a neuroprotective effects.Impact of TREM2 functional mutations on microglial phagocytosis is associated with an increased risk of neurodegenerative diseases such as AD and Parkinson's disease.Therefore,understanding the role of TREM2-mediated phagocytic clearance of microglia in different neurodegenerative diseases is of great significance for exploring new therapeutic directions for neurodegenerative diseases.