Bai Shuju, Wang Wenbo, Zhang Zhiwei, Li Mengyao, Chen Zehan, Wang Jiuqiao, Zhao Yanlin, An Lu, Wang Yuxiang, Xing Shu, Fu Xueqi, Ma Junfeng
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.
School of Mathematics, Jilin University, Changchun, China.
Front Aging Neurosci. 2021 Nov 12;13:762659. doi: 10.3389/fnagi.2021.762659. eCollection 2021.
Amyloid-β, a hallmark of Alzheimer's disease, forms toxic intracellular oligomers and extracellular senile plaques resulting in neuronal toxicity. Ethanol is widely consumed worldwide. Moderate ethanol consumption has numerous benefits in humans. We found that ethanol could significantly extend the lifespan of in a previous study. Based on that study, we tested the effect of ethanol on Alzheimer's disease transgenic strain CL4176, which expresses amyloid-β1-42 peptide in body wall muscle cells. Ethanol delayed paralysis and reduced amyloid-β oligomers in worms of the CL4176 strain. Moreover, ethanol could induce the nuclear translocation of DAF-16 in the nematodes. However, in worms that were fed RNAi bacteria, ethanol no longer delayed the paralysis. The qPCR assays showed that ethanol increases the expression of , and their common target genes- small heat shock protein genes. In addition, we also found that ethanol could increase lysosome mass in the CL4176 worms. In summary, our study indicated that ethanol attenuated amyloid-β toxicity in the Alzheimer's disease model of via increasing the level of lysosomes to promote amyloid-β degradation and upregulating the levels of small heat shock protein genes to reduce amyloid-β aggregation.
淀粉样蛋白β是阿尔茨海默病的一个标志，会形成有毒的细胞内寡聚体和细胞外老年斑，从而导致神经元毒性。乙醇在全球范围内被广泛饮用。适度饮用乙醇对人体有诸多益处。在之前的一项研究中，我们发现乙醇可以显著延长线虫的寿命。基于该研究，我们测试了乙醇对阿尔茨海默病转基因线虫品系CL4176的影响，该品系在体壁肌肉细胞中表达淀粉样蛋白β1-42肽。乙醇延缓了CL4176品系线虫的麻痹并减少了淀粉样蛋白β寡聚体。此外，乙醇可诱导线虫中DAF-16的核转位。然而，在用RNAi细菌喂养的线虫中，乙醇不再延缓麻痹。qPCR分析表明，乙醇增加了hsp-16.2、hsp-16.4及其共同靶基因——小热休克蛋白基因的表达。此外，我们还发现乙醇可增加CL4176线虫中的溶酶体质量。总之，我们的研究表明，乙醇通过提高溶酶体水平以促进淀粉样蛋白β降解，并上调小热休克蛋白基因水平以减少淀粉样蛋白β聚集，从而减轻了线虫阿尔茨海默病模型中的淀粉样蛋白β毒性。
