期刊
ADVANCED SCIENCE
卷 9, 期 17, 页码 -出版社
WILEY
DOI: 10.1002/advs.202104986
关键词
AKT3; grey matter lesions; IL-10RA; microRNAs; miR-15a; 16-1; vascular cognitive impairment and dementia; white matter lesions
资金
- National Institutes of Health [NS112181]
- Department of Veterans Affairs [I01BX004837]
The study found that knockout mice of miR-15a/16-1 exhibited fewer cognitive and sensorimotor deficits after VCID. The deficiency of miR-15a/16-1 also reduced myelin degeneration, axonal injury, and neuronal loss in VCID mice. The miR-15a/16-1-IL/10RA/AKT3 axis played a critical role in regulating vascular brain damage and cognitive decline after VCID. Targeting miR-15a/16-1 could be a novel therapeutic approach for the treatment of VCID.
Chronic cerebral hypoperfusion-derived brain damage contributes to the progression of vascular cognitive impairment and dementia (VCID). Cumulative evidence has shown that microRNAs (miRs) are emerging as novel therapeutic targets for CNS disorders. In this study, it is sought to determine the regulatory role of miR-15a/16-1 in VCID. It is found that miR-15a/16-1 knockout (KO) mice exhibit less cognitive and sensorimotor deficits following VCID. Genetic deficiency of miR-15a/16-1 in VCID mice also mitigate myelin degeneration, axonal injury, and neuronal loss. Mechanistically, miR-15a/16-1 binds to the 3'-UTR of AKT3 and IL-10RA. Genetic deletion of miR-15a/16-1 increases AKT3 and IL-10RA expression in VCID brains, and intranasal delivery of AKT3 and IL-10RA siRNA-loaded nanoparticles partially reduce brain protection and cognitive recovery in miR-15a/16-1 KO mice after VCID. In conclusion, the miR-15a/16-1-IL/10RA/AKT3 axis plays a critical role in regulating vascular brain damage and cognitive decline after VCID. Targeting miR-15a/16-1 is a novel therapeutic approach for the treatment of VCID.
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