Journal
THERANOSTICS
Volume 11, Issue 9, Pages 4103-4121Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.53418
Keywords
microRNA-146a; Alzheimer's disease; microglial polarization; neuroinfammation; phagocytic activity
Categories
Funding
- National Natural Science Foundation of China [81671181]
- Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme
Ask authors/readers for more resources
Alzheimer's disease has no effective treatment, with research focused on Aβ and Tau. Abnormal microglial polarization is a key feature in the progression of AD, affecting neuroprotective functions. MiR-146a shows promise in opposing AD by switching microglial phenotypes and reducing neuroinflammation.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and currently has no effective treatment. Mainstream research on the mechanisms and therapeutic targets of AD is focused on the two most important hallmarks, A beta and Tau, but the results from clinical studies are not encouraging. Abnormal microglial polarization is a clear typical pathological feature in the progression of AD. Microglia can be neuroprotective by degrading and removing A beta and Tau. However, under AD conditions, microglia transform into a pro-inflammatory phenotype that decreases the phagocytic activity of microglia, damages neurons and promotes the pathology of AD. We previously reported that a miR-146a polymorphism is associated with sporadic AD risk, and the nasal administration of miR-146a mimics reduced cognitive impairment and the main pathological features of AD. However, it is not clear by what mechanism miR-146a resists the pathological process of AD. In this study, we discovered that microglia-specific miR-146a overexpression reduced cognitive deficits in learning and memory, attenuated neuroinflammation, reduced A beta levels, ameliorated plaque-associated neuritic pathology, and prevented neuronal loss in APP/PS1 transgenic mice. In addition, we found that miR-146a switched the microglial phenotype, reduced pro-inflammatory cytokines and enhanced phagocytic function to protect neurons in vitro and in vivo. Moreover, transcriptional analysis confirmed that miR-146a opposed the pathological process of AD mainly through neuroinflammation-related pathways. In summary, our results provide sufficient evidence for the mechanism by which miR-146a opposes AD and strengthen the conclusion that miR-146a is a promising target for AD and other microglia-related diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available