| First Author | Yin H | Year | 2023 |
| Journal | PLoS Biol | Volume | 21 |
| Issue | 3 | Pages | e3002017 |
| PubMed ID | 36881554 | Mgi Jnum | J:346277 |
| Mgi Id | MGI:7443658 | Doi | 10.1371/journal.pbio.3002017 |
| Citation | Yin H, et al. (2023) Loss of the m6A methyltransferase METTL3 in monocyte-derived macrophages ameliorates Alzheimer's disease pathology in mice. PLoS Biol 21(3):e3002017 |
| abstractText | Alzheimer's disease (AD) is a heterogeneous disease with complex clinicopathological characteristics. To date, the role of m6A RNA methylation in monocyte-derived macrophages involved in the progression of AD is unknown. In our study, we found that methyltransferase-like 3 (METTL3) deficiency in monocyte-derived macrophages improved cognitive function in an amyloid beta (Abeta)-induced AD mouse model. The mechanistic study showed that that METTL3 ablation attenuated the m6A modification in DNA methyltransferase 3A (Dnmt3a) mRNAs and consequently impaired YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated translation of DNMT3A. We identified that DNMT3A bound to the promoter region of alpha-tubulin acetyltransferase 1 (Atat1) and maintained its expression. METTL3 depletion resulted in the down-regulation of ATAT1, reduced acetylation of alpha-tubulin and subsequently enhanced migration of monocyte-derived macrophages and Abeta clearance, which led to the alleviated symptoms of AD. Collectively, our findings demonstrate that m6A methylation could be a promising target for the treatment of AD in the future. |
