Hu Xiqi, Ma Ya-Nan, Peng Jun, Wang Zijie, Liang Yuchang, Xia Ying
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, China.
Biosci Trends. 2025 May 9;19(2):189-201. doi: 10.5582/bst.2025.01065. Epub 2025 Mar 18.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, and endoplasmic reticulum (ER) stress. In recent years, exosomes have garnered significant attention as a potential therapeutic tool for neurodegenerative diseases. This study, for the first time, investigates the neuroprotective effects of exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-Exos) in AD and further explore the potential role of low-density lipoprotein receptor-related protein 1 (LRP1) in this process. Using an Aβ1-42-induced AD mouse model, we observed that OM-MSCs-Exos significantly improved cognitive function in behavioral tests, reduced neuroinflammatory responses, alleviated ER stress, and decreased neuronal apoptosis. Further analysis revealed that OM-MSCs-Exos exert neuroprotective effects by modulating the activation of microglia and astrocytes and influencing the ER stress response, a process that may involve LRP1. Although these findings support the potential neuroprotective effects of OM-MSCs-Exos, further studies are required to explore their long-term stability, dose dependency, and immunogenicity to assess their feasibility for clinical applications.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为认知功能下降、神经炎症和内质网（ER）应激。近年来，外泌体作为神经退行性疾病的一种潜在治疗工具受到了广泛关注。本研究首次探讨了嗅黏膜间充质干细胞来源的外泌体（OM-MSCs-Exos）对AD的神经保护作用，并进一步探究了低密度脂蛋白受体相关蛋白1（LRP1）在此过程中的潜在作用。利用Aβ1-42诱导的AD小鼠模型，我们观察到OM-MSCs-Exos在行为测试中显著改善了认知功能，减轻了神经炎症反应，缓解了ER应激，并减少了神经元凋亡。进一步分析表明，OM-MSCs-Exos通过调节小胶质细胞和星形胶质细胞的激活以及影响ER应激反应发挥神经保护作用，这一过程可能涉及LRP1。尽管这些发现支持了OM-MSCs-Exos的潜在神经保护作用，但仍需进一步研究来探索其长期稳定性、剂量依赖性和免疫原性，以评估其临床应用的可行性。
