Astrocytic Mettl14 Depletion Enhances Cognitive Function By Attenuating Astrogliosis Via The Dusp1mapk Pathway In Appps1 Mice Targeting Neuroinflammation In Alzheimerâtms Disease Yan Teng Jianli Xu Shu He Jin Yi Manjun Li Qin Tang Xingmin Chen Fan Wei Yanzhuo Liu Haisong Jiang Yang Xiang Jialing Zhao Jing Yang Weidong Le Min Zheng Lu Yang by Yan Teng & Jianli Xu & Shu He & Jin Yi & Manjun Li & Qin Tang & Xingmin Chen & Fan Wei & Yanzhuo Liu & Haisong Jiang & Yang Xiang & Jia-ling Zhao & Jing Yang & Weidong Le & Min Zheng & Lu Yang instant download after payment.

Alzheimer’s disease (AD), a leading cause of dementia, represents a critical unmet global medical need. While the precisemechanisms underlying AD pathogenesis remain elusive, increasing evidence underscores the pivotal role of neuroinflammation indriving cognitive impairment. N6-methyladenosine (m6A), an epigenetic modification regulating RNA metabolism, has been found1234567890();,:to be dysregulated in AD. In this study, we used a Mettl14 conditional knockout APP/PS1 mouse model (AD-cKO mice) toinvestigate the effects of modulating astrocytic m6A levels on AD progression. Our comprehensive histological, biochemical, andtranscriptomic analyses revealed that AD-cKO mice exhibited enhanced cognitive function, along with decreased astrogliosis andreduced neuroinflammation when compared to APP/PS1 control mice. Based on the conjoint analysis of MeRIP-seq and RNA-seqdata, our mechanistic studies further demonstrated that the loss of Mettl14 in astrocytes significantly affected the expression ofDUSP1, a negative regulator of inflammation, to mitigate MAPK signaling. These findings suggest that targeting m6A regulators,such as Mettl14, may represent a promising therapeutic strategy to control neuroinflammation in AD progression. This study alsohighlights the broader potential of epigenetic modulation as a novel approach for treating AD.Molecular Psychiatry;