| First Author | Koh HS | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 23 | PubMed ID | 34884940 |
| Mgi Jnum | J:348159 | Mgi Id | MGI:6833353 |
| Doi | 10.3390/ijms222313136 | Citation | Koh HS, et al. (2021) Targeting MicroRNA-485-3p Blocks Alzheimer's Disease Progression. Int J Mol Sci 22(23) |
| abstractText | Alzheimer's disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction. With only one FDA-approved therapy, effective treatment strategies for AD are urgently needed. In this study, we found that microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues, cerebrospinal fluid, and plasma of patients with AD, and its antisense oligonucleotide (ASO) reduced Abeta plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. Mechanistically, miR-485-3p ASO enhanced Abeta clearance via CD36-mediated phagocytosis of Abeta in vitro and in vivo. Furthermore, miR-485-3p ASO administration reduced apoptosis, thereby effectively decreasing truncated tau levels. Moreover, miR-485-3p ASO treatment reduced secretion of proinflammatory cytokines, including IL-1beta and TNF-alpha, and eventually relieved cognitive impairment. Collectively, our findings suggest that miR-485-3p is a useful biomarker of the inflammatory pathophysiology of AD and that miR-485-3p ASO represents a potential therapeutic candidate for managing AD pathology and cognitive decline. |
