ESCRT机制对阿尔茨海默病作用的研究进展

Research Progress in Role of ESCRT Machinery in Alzheimer′s Disease

阿尔茨海默病(AD)是人类衰老过程中影响老年人智力、自理能力以及致残和新的致死病因的重大疾病之一。神经元中tau蛋白的过度磷酸化以及β淀粉样蛋白(Aβ)的沉积是AD发病的主要假说,目前仍无有效治疗AD的方案。转运必需内体分选复合物(ESCRT)在蛋白质降解及维持细胞结构完整、功能稳定方面发挥重要作用。ESCRT识别分类泛素化的病理tau蛋白及Aβ产生多囊泡体进入溶酶体降解或分泌,从而减轻tau蛋白及Aβ的神经元毒性作用。此外,ESCRT还能修复神经元突触的损伤,减少神经元的凋亡。因此,ESCRT机制的研究可能为治疗和延缓AD的进展提供新的研究思路和方向。

Alzheimer′s disease(AD)is one of the major diseases affecting the intelligence,self-care ability,disability and new cause of death in the aging process of human beings.Hyperphosphorylation of tau protein and deposition of amyloidβ-protein(Aβ)in neurons are the main hypotheses for the pathogenesis of AD.At present,there is still no effective treatment for AD.The endosomal sorting complex required for transport(ESCRT)plays an important role in protein degradation and maintenance of cell structural integrity and functional stability.ESCRT recognizes and classifies ubiquitinated pathological tau and Aβto produce multivesicular body into lysosomes for degradation or secretion,thereby alleviating the neuronal toxicity of pathological tau and Aβ.In addition,ESCRT can repair synaptic damage and reduce neuronal apoptosis.Therefore,the study of ESCRT machinery may provide new research ideas and directions for the treatment and progression delaying of AD.