阿尔茨海默症 z-bo 2020-09-19 352

　　Under the guidance of Professor Le, Dr. Hui Liu and his colleagues studied the effect of chronic hypoxia on the etiology of Alzheimer's disease (AD), and looked at its pathogenesis from an epigenetic perspective. As an important environmental factor, chronic hypoxia can affect the development of AD at all stages of life. In previous research by Professor Le’s team, chronic hypoxia aggravated the formation of senile plaques in the brains of AD mice, and chronic intermittent hypoxia during pregnancy was associated with the impairment of learning and memory in the offspring of AD mice. We have confirmed that it may aggravate the accumulation of age spots. 

　　"In addition, hypoxia can change the histone modification of the NEP promoter, down-regulate the expression of NEP, thereby reducing the degradation of Aβ, thereby allowing hypoxia to regulate gene expression through epigenetic modification. Suggest. Based on the above findings, in this study, the authors studied the effects of chronic hypoxia on the behavior of APPSwe/PS1dE9 transgenic mice and the development of AD-related neuropathology and DNA methylation. Study the mechanism of possible effects from the perspective of modification. Compared with mice without chronic hypoxia, they showed decreased spatial learning and memory in chronic hypoxic mice, increased senile plaque formation, increased Aβ production, and AD-related neuropathology (including tau). Increased protein phosphorylation and decreased synaptic vesicles indicate a worsening of the phenotype; epigenetic analysis shows that chronic hypoxia can reduce the expression of DNA methyltransferase 3b (DNMT3b) in the brain of mice. This reduces the level of genomic DNA methylation and down-regulates the methylation level of the promoter regions of genes related to gamma-cutting enzyme components (PS1, PEN2, NCT, etc.), thereby down-regulating the protein levels of these genes . Further affect expression. Through epigenetic intervention, up-regulation of DNMT3b can reverse these changes.

　　These findings indicate that chronic hypoxia may aggravate AD by down-regulating DNMT3b. The results of the study indicate that chronic hypoxia is a risk factor for AD, further elucidating the molecular mechanism of DNA methylation modification. The results not only support the belief that environmental factors can stimulate and aggravate AD, but also provide new ideas for the treatment of AD and provide a basis for early prevention of AD. In the future, adjusting the metamorphosis of the organism may provide a new breakthrough for AD treatment.