高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

硒唑甲酰胺类Src激酶抑制剂对阿尔茨海默病中Aβ诱导的毒性作用的研究

吴浩1,王磊1,刘洋1,张芯玮1,潘新靓1,张名杰1,江凤瑜1,肖军海2,林凤1   

  1. 1. 吉林大学生命科学学院

    2. 中国人民解放军军事科学院军事医学研究院

  • 收稿日期:2026-06-21 修回日期:2026-07-16 出版日期:2026-07-27 发布日期:2026-07-27
  • 通讯作者: 林凤 E-mail:linfeng@jlu.edu.cn
  • 基金资助:

    中国吉林省科技厅自然科学基金会（批准号：20220101268JC）资助

Selenazole Carboxamide Src Kinase Inhibitor against Aβ-Induced Toxicity in Alzheimer’s Disease

Hao Wu1, Lei Wang1, Yang Liu1, Xinwei Zhang1, Xinliang Pan1, Mingjie Zhang1, Fengyu Jiang1, Junhai Xiao2, Feng Lin1   

  1. 1. School of Life Sciences, Jilin University

    2. Academy of Military Medical Sciences, Academy of Military Sciences

  • Received:2026-06-21 Revised:2026-07-16 Online:2026-07-27 Published:2026-07-27
  • Contact: Feng Lin E-mail:linfeng@jlu.edu.cn
  • Supported by:

    Supported by the Natural Science Foundation of Science and Technology Agency of Jilin Province of China (No. 20220101268JC)

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摘要： 本研究旨在探讨Src酪氨酸蛋白激酶抑制剂（SAFA320）对转基因秀丽隐杆线虫CL4176的神经保护作用及其机制. 在本研究中，与空白对照相比， SAFA320处理显著减少了CL4176线虫中β淀粉样蛋白（Aβ）寡聚体的沉积，从而降低了线虫的瘫痪率，并能有效降低其体内活性氧（ROS）的产生，CL4176线虫组织内Src激酶活性也显著降低. 荧光实时定量PCR结果显示，SAFA320处理导致CL4176线虫体内skn-1基因及其下游靶基因gst-4的表达显著上调，说明化合物SAFA320通过调节CL4176线虫中的SKN-1信号通路从而达到抑制Aβ毒性的效果. 综上所述，SAFA320在缓解CL4176线虫的Aβ毒性和改善认知功能方面具有显著效果，是一种潜在的抗AD候选药物.

关键词:

阿尔茨海默病, Src激酶抑制剂（SAFA320）, β淀粉样蛋白, skn-1, 秀丽隐杆线虫

Abstract: The study aimed to investigate the effects of Src tyrosine protein kinase inhibitor (SAFA320) on transgenic Caenorhabditis elegans CL4176, as well as its possible mechanism. In the study, C. elegans CL4176 adminstrated with SAFA320 could reduce the deposition of Aβ oligomer to alleviate nematode paralysis, and decrease ROS production. Results of tissue Src kinase activity spectrophotometry analysis showed that SAFA320 could reduce the activities of Src in C. elegans. Meanwhile, the genes expression of skn-1 and its downstream target gene gst-4 were significantly increased, suggesting that compound inhibited Aβ toxicity may involve in SKN-1 signaling pathway in CL4176. In conclusion，SAFA320 is effective in alleviating Aβ toxicity and improving cognitive functions in C. elegans CL4176, and it is a potent candidate agent against AD.

Key words:

Alzheimer’s disease,  , Src inhibitor (SAFA320),  , amyloid beta,  , skn-1,  , Caenorhabditis elegans

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