| First Author | Li B | Year | 2024 |
| Journal | Neural Regen Res | Volume | 19 |
| Issue | 7 | Pages | 1593-1601 |
| PubMed ID | 38051904 | Mgi Jnum | J:357482 |
| Mgi Id | MGI:7763714 | Doi | 10.4103/1673-5374.385839 |
| Citation | Li B, et al. (2024) Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease. Neural Regen Res 19(7):1593-1601 |
| abstractText | Mitochondrial dysfunction is a hallmark of Alzheimer's disease. We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of APP/PS1 mice. Because Alzheimer's disease affects the entire brain, further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole. Here, we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing, immunostaining, and lightsheet imaging to clarify their spatial distribution. Additionally, to clarify whether the sirtuin 1 (SIRT1)-related pathway plays a regulatory role in neural stem cell-derived exosomes interfering with mitochondrial functional changes, we generated a novel nervous system-SIRT1 conditional knockout APP/PS1 mouse model. Our findings demonstrate that neural stem cell-derived exosomes significantly increase SIRT1 levels, enhance the production of mitochondrial biogenesis-related factors, and inhibit astrocyte activation, but do not suppress amyloid-beta production. Thus, neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer's disease that activates the SIRT1-PGC1alpha signaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis. In addition, we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer's disease, and that neural stem cell-derived exosome treatment can reverse this effect, indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis. |
