ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Neuroplasticity and Development
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1688694
PGC-1α promotes the survival of newborn neurons within AD hippocampus through activation of the FNDC5/BDNF/TrkB signaling pathway
Provisionally accepted
- Jiangsu University, Zhenjiang, China
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The dysfunction in learning and memory observed in Alzheimer's disease (AD) is strongly associated with impaired neurogenesis in the hippocampal region. Our previous research has underscored the potential of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in alleviating the pathological abnormalities linked to AD. As a pervasive metabolic regulator, high levels of PGC-1α are found in energetically demanding tissues like the hippocampus. However, the precise role and underlying mechanisms by which PGC-1α regulates neurogenesis within the AD-affected hippocampus remain incompletely elucidated. In this study, we induced overexpression of PGC-1α by microinfusing rAAV2-CMV-Ppargc1a-m-FLAG-HA into the dentate gyrus (DG) region of the hippocampus in APP/PS1 mice. Our findings revealed that PGC-1 α promotes the proliferation and survival of newly generated neurons in the hippocampus affected by AD. Furthermore, our findings demonstrated that PGC-1α functions as an upstream regulator of the FNDC5-BDNF-TrkB signaling pathway, and its knockdown inhibits neuronal proliferation via this pathway. Collectively, these findings indicate that PGC-1α functions as a critical effector in the FNDC5-BDNF-TrkB signaling pathway within newborn neurons. Enhancing PGC-1α levels, either pharmacologically or via alternative strategies, may thus represent a promising therapeutic avenue for AD.
Keywords: PGC-1α, Alzheimer's disease, newborn neurons, BDNF, Survival
Received: 19 Aug 2025; Accepted: 26 Sep 2025.
Copyright: © 2025 Wang, Wang, Zhang, Pan, Wang, Wang, Qian, Liu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jia Wang, wangjia@ujs.edu.cn
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