Research Centre for Medical Genetics, Moscow 115522, Russia.
Research Institute of Molecular and Cellular Medicine of the Medical Institute Peoples' Friendship, University of Russia, Moscow 117198, Russia.
Int J Mol Sci. 2024 Nov 18;25(22):12378. doi: 10.3390/ijms252212378.
Alzheimer's disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis.
阿尔茨海默病是一种进行性神经退行性疾病,其特征是线粒体功能障碍、β-淀粉样斑块积累以及脑中过度磷酸化的 tau 缠结,导致记忆丧失和认知缺陷。目前这种疾病尚无治愈方法,但干细胞在神经退行性病变治疗中的潜力正在积极研究中。本综述讨论了使用小鼠模型和人类患者进行的临床前和临床研究,以调查新型干细胞治疗方法的应用。研究结果为基于干细胞的治疗应用提供了有价值的见解,包括使用神经细胞、神经胶质细胞、间充质细胞、胚胎细胞和诱导多能干细胞。我们介绍了干细胞替代治疗的当前研究,其中细胞可以功能性地整合到神经网络中,替代受损的神经元,并增强大脑中受损的突触回路。我们探讨了干细胞通过分泌因子发挥旁分泌作用,诱导神经再生和改变炎症反应。我们专注于外泌体的神经保护功能以及它们的神经发生和突触发生作用。我们研究了通过隧道纳米管进行的线粒体穿梭,通过恢复受损细胞的正常功能、改善其代谢并降低细胞凋亡水平,从而实现健康线粒体的转移。