| Autor: |
Bo Li, Yujie Chen, Yan Zhou, Xuanran Feng, Guojun Gu, Shuang Han, Nianhao Cheng, Yawen Sun, Yiming Zhang, Jiahui Cheng, Qi Zhang, Wei Zhang, Jianhui Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Neural Regeneration Research, Vol 19, Iss 7, Pp 1593-1601 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1673-5374 |
| DOI: |
10.4103/1673-5374.385839 |
| Popis: |
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-β production. Thus, neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1α 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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