文献类型：期刊文献

英文题名：N-Salicyloyl Tryptamine Derivatives Improve Mitochondrial Function To Treat Alzheimer's Disease

作者：Zeng, Jing[1];Zhao, Yuting[1];Chen, Yaxin[1];Wu, Kun[1];Yang, Changlei[1];Wu, Ying[1];Pang, Guanglong[2];Zhang, Miao[1];Wen, Huaixiu[3,4];Wang, Zhen[1,5,6,7,8];Peng, Xue[1]

第一作者：Zeng, Jing

通信作者：Wang, Z[1];Peng, X[1];Wen, HX[2];Wen, HX[3];Wang, Z[4];Wang, Z[5];Wang, Z[6];Wang, Z[7]

机构：[1]Univ South China, Sch Pharmaceut Sci, Sch Basic Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China;[2]Gansu Univ Chinese Med, Gansu Prov Hosp, Clin Med Coll 1, Lanzhou 730000, Peoples R China;[3]Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Peoples R China;[4]Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Tibetan Med Res, Xining 810008, Peoples R China;[5]Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Thorac & Cardiovasc Surg, Hengyang 421001, Hunan, Peoples R China;[6]Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Oncol, Hengyang 421001, Hunan, Peoples R China;[7]Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China;[8]Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Changsha 410008, Hunan, Peoples R China

第一机构：Univ South China, Sch Pharmaceut Sci, Sch Basic Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China

通信机构：[1]corresponding author), Univ South China, Sch Pharmaceut Sci, Sch Basic Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China;[2]corresponding author), Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Peoples R China;[3]corresponding author), Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Tibetan Med Res, Xining 810008, Peoples R China;[4]corresponding author), Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Thorac & Cardiovasc Surg, Hengyang 421001, Hunan, Peoples R China;[5]corresponding author), Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Oncol, Hengyang 421001, Hunan, Peoples R China;[6]corresponding author), Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China;[7]corresponding author), Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Changsha 410008, Hunan, Peoples R China.

年份：2026

卷号：11

期号：7

起止页码：12479

外文期刊名：ACS OMEGA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001685269600001)】；

基金：We gratefully acknowledge the financial support from the Hunan Provincial Natural Science Foundation of China (No. 2023JJ30527 and No. 2024JJ6394), Scientific Research Foundation of Hunan Provincial Education Department (No. 23A0319 and No. 23B0446), Supported by University of South China Innovation Foundation for Postgraduate (No. 243YXC031), Postgraduate Scientific Research Innovation Project of Hunan Province (No. CX20251475), College Students Innovation and Entrepreneurship Training Program of Hunan Province (No. D202405251556232838).

语种：英文

摘要：Alzheimer's disease (AD) is a neurodegenerative disease (NDD) characterized by complex pathogenesis and remains incurable to date. Emerging evidence has demonstrated that mitochondrial dysfunction not only serves as a central component in AD initiation but also precedes other pathological processes, thereby playing a pivotal role in both the pathogenesis and progression of AD. Previous studies have confirmed that N-salicyloyl tryptamine derivatives can regulate mitochondrial function and effectively treat NDDs. Among them, compound N2 showed the best efficacy. This study first applied compound N2 to the treatment of AD and confirmed that it exerts anti-AD effects by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and enhancing the activity of mitochondrial complex I (MCI). The results showed that N2 improved mitochondrial dysfunction and neuro-inflammation in PC12 or BV2 cells. N2 was also shown to alleviate anxiety, cognitive impairment, neuronal damage, and amyloid-beta (A beta) pathological deposition in scopolamine-induced male Kunming mice. Mechanistic studies indicate that N2 can reverse mitochondrial damage induced by rotenone (MCI inhibitor), as evidenced by reduced ROS levels and increased ATP levels; it also upregulates Nrf2 protein expression. These findings collectively indicate that N2 is a highly valuable anti-AD mitochondrial function regulator, providing a new strategy for the efficient treatment of AD.