Thrombospondin-1 prevents Aβ-mediated synaptic pathology in Alzheimer’s disease

Alzheimer’s disease;amyloid beta;thrombospondin;synaptic pathology;spine;synaptic plasticity;5xFAD;Tg2576;animal model;autophagy;astrocyte;575

자연과학대학 협동과정유전공학전공 ;

University:서울대학교 대학원

关键词: Alzheimer’s disease;    amyloid beta;    thrombospondin;    synaptic pathology;    spine;    synaptic plasticity;    5xFAD;    Tg2576;    animal model;    autophagy;    astrocyte;    575;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/131156/1/000000008788.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

Alzheimer’s disease (AD) is characterized by cognitive dysfunction and memory loss, which are often the result of synaptic pathology. Thrombospondin (TSP) is an astrocyte-secreted protein well-known for its function as an anti-angiogenic role. Recently, however, the role of TSP as a modulator of synaptogenesis and neurogenesis has been highlighted. Here, I studied the role of one of the five TSP isoforms, TSP-1, in vitro and in AD animal models. TSP-1 release was decreased by Aβ42 in vitro and the reduced level of TSP-1 was observed in both 5xFAD and Tg2576 mice. Synaptic pathology caused by Aβ42 such as decreased dendritic density, impaired vesicle recycling, and reduced long-term potentiation (LTP) were prevented by co-incubation with TSP-1 and Aβ. TSP-1 is a potential therapeutic component against the damaging effects caused by Aβ42 in AD pathogenesis.