Dynamic changes of autophagic flux induced by Abeta in the brain of postmortem Alzheimer's disease patients, animal models and cell models
Dynamic changes of autophagic flux induced by Abeta in the brain of postmortem Alzheimer's disease patients, animal models and cell models
复制标题
阿尔茨海默病死后患者、动物模型和细胞模型大脑中 Abeta 诱导的自噬通量的动态变化
DOI：
10.18632/aging.103305
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发表时间：
2020-06-15
期刊：
影响因子：
5.2
通讯作者：
He, Guiqiong
中科院分区：
文献类型：
--
作者：
Long, Zhimin;Chen, Jingfei;He, Guiqiong
Autophagy has been reported to play a dual "double-edged sword" role in the occurrence and development of Alzheimer's disease (AD). To assess the relationship between AD and autophagy, the dynamic changes of autophagic flux in the brain of postmortem AD patients, animal models and cell models were studied. The results showed that autophagosomes (APs) accumulation and expression of lysosomal markers were decreased in the brains of AD patients. In the brain of APP/PS1 double transgenic mice, APs did not accumulate before the formation of SPs but accumulated along with the deposition of SPs, as well as the level of lysosomal markers cathepsin B and Lamp1 protein decreased significantly. In the brains of APP/PS1/LC3 triple - transgenic mice, the number of APs increased with age, but the number of ALs did not increase accordingly. The activation of autophagy is mainly due to the increase in A beta rather than the overexpression of mutated APP gene. However, both the treatment with exogenous A beta(25-35) and the mutation of the endogenous APP gene blocked the fusion of APs with lysosomes and decreased lysosomal functioning in AD model cells, which may be the main mechanism of autophagy dysregulation in AD.
