Li Jiao, Cui Xiaodong, Ma Xiaoli, Wang Zhuanhua
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, PR China.
College of Life Science, Shanxi University, Taiyuan 030006, PR China.
Exp Gerontol. 2017 Mar;89:78-86. doi: 10.1016/j.exger.2017.01.018. Epub 2017 Jan 22.
Alzheimer's disease (AD) is an age-related neurodegenerative disease, of which β-amyloid (Aβ) induced toxicity was suggested as a main cause. Some substances with prolongevity effects have been shown to be protective against AD. In a previous study we demonstrated that a recombinant buckwheat trypsin inhibitor (rBTI) could prolonge the lifespan in Caenorhabditis elegans (C. elegans). Here, we investigated whether rBTI may benefit to mitigate the AD symptom by feeding the AD model C. elegans CL4176. CL4176 is a transgenic C. elegans expressing human Aβ in muscle tissue. The results showed that rBTI not only could extend lifespan but also could reduce Aβ toxicity-triggered body paralysis in AD worms. Further study found the accumulation of Aβ was decreased and autophagy-lysosomal degradation pathway was activated in AD worms treated with rBTI. Moreover, the inhibition of autophagy reduced rBTI-mediated paralysis delay. Genetic analyses showed rBTI increased the transcriptional activity of dauer formation abnormal-16 (DAF-16) and the disruption of daf-16 abolished rBTI-mediated protective effect in AD worms. Taken together, these data indicated that rBTI promoted the autophagy-lysosomal degradation pathway to reduce the Aβ-induced toxicity via DAF-16 in an AD model C. elegans, implying that BTI has the potential to protect against AD.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病，其中β-淀粉样蛋白（Aβ）诱导的毒性被认为是主要病因。一些具有延长寿命作用的物质已被证明对AD具有保护作用。在先前的一项研究中，我们证明了重组荞麦胰蛋白酶抑制剂（rBTI）可以延长秀丽隐杆线虫（C. elegans）的寿命。在此，我们通过喂食AD模型秀丽隐杆线虫CL4176来研究rBTI是否有助于减轻AD症状。CL4176是一种在肌肉组织中表达人Aβ的转基因秀丽隐杆线虫。结果表明，rBTI不仅可以延长寿命，还可以减少AD线虫中Aβ毒性引发的身体麻痹。进一步研究发现，在用rBTI处理的AD线虫中，Aβ的积累减少，自噬-溶酶体降解途径被激活。此外，自噬的抑制减少了rBTI介导的麻痹延迟。基因分析表明，rBTI增加了 dauer形成异常-16（DAF-16）的转录活性，而daf-16的破坏消除了rBTI在AD线虫中的介导保护作用。综上所述，这些数据表明，在AD模型秀丽隐杆线虫中，rBTI通过DAF-16促进自噬-溶酶体降解途径，以降低Aβ诱导的毒性，这意味着BTI具有预防AD的潜力。
