Parkinson＇s disease （PD） is pathologically characterized by the presence of α-synuclein （α-syn）-positive intra-cytoplasmic inclusions named Lewy bodies in the dopaminergic neurons of the substantia nigra. A ser...Parkinson＇s disease （PD） is pathologically characterized by the presence of α-synuclein （α-syn）-positive intra-cytoplasmic inclusions named Lewy bodies in the dopaminergic neurons of the substantia nigra. A series of morbid consequences are caused by pathologically high amounts or mutant forms of α-syn, such as defects of membrane trafficking and lipid metabolism. In this review, we consider evidence that both point mutation and overexpression of α-syn result in aberrant degradation in neurons and microglia, and this is associated with the autophagy-lysosome pathway and endosome-lysosome system, leading directly to pathological intracellular aggregation, abnormal externalization and re-internalization cycling （and, in turn, internalization and re-externalization）, and exocytosis. Based on these pathological changes, an increasing number of researchers have focused on these new therapeutic targets, aiming at alleviating the pathological accumulation of α-syn and re-establishing normal degradation.展开更多
基金supported by the National Program of Basic Research of China(2010CB945200, 2011CB504104)the National Natural Science Foundation of China (30700888, 30770732,30872729, 30971031)+2 种基金the Key Discipline Program of Shanghai Municipality (S30202)the Shanghai Key Project of Basic Science Research (10411954500)the Program for Outstanding Medical Academic Leaders of Shanghai Municipality, China (LJ 06003)
文摘Parkinson＇s disease （PD） is pathologically characterized by the presence of α-synuclein （α-syn）-positive intra-cytoplasmic inclusions named Lewy bodies in the dopaminergic neurons of the substantia nigra. A series of morbid consequences are caused by pathologically high amounts or mutant forms of α-syn, such as defects of membrane trafficking and lipid metabolism. In this review, we consider evidence that both point mutation and overexpression of α-syn result in aberrant degradation in neurons and microglia, and this is associated with the autophagy-lysosome pathway and endosome-lysosome system, leading directly to pathological intracellular aggregation, abnormal externalization and re-internalization cycling （and, in turn, internalization and re-externalization）, and exocytosis. Based on these pathological changes, an increasing number of researchers have focused on these new therapeutic targets, aiming at alleviating the pathological accumulation of α-syn and re-establishing normal degradation.
