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Publication : The role of m6A modification in the risk prediction and Notch1 pathway of Alzheimer's disease.

First Author  Qiao Y Year  2024
Journal  iScience Volume  27
Issue  7 Pages  110235
PubMed ID  39040060 Mgi Jnum  J:352150
Mgi Id  MGI:7704767 Doi  10.1016/j.isci.2024.110235
Citation  Qiao Y, et al. (2024) The role of m6A modification in the risk prediction and Notch1 pathway of Alzheimer's disease. iScience 27(7):110235
abstractText  N6-methyladenosine (m6A) methylation and abnormal immune responses are implicated in neurodegenerative diseases, yet their relationship in Alzheimer's disease (AD) remains unclear. We obtained AD datasets from GEO databases and used AD mouse and cell models, observing abnormal expression of m6A genes in the AD group, alongside disruptions in the immune microenvironment. Key m6A genes (YTHDF2, LRPPRC, and FTO) selected by machine learning were associated with the Notch pathway, with FTO and Notch1 displaying the strongest correlation. Specifically, FTO expression decreased and m6A methylation of Notch1 increased in AD mouse and cell models. We further silenced FTO expression in HT22 cells, resulting in upregulation of the Notch1 signaling pathway. Additionally, increased Notch1 expression in dendritic cells heightened inflammatory cytokine secretion in vitro. These results suggest that reduced FTO expression may contribute to the pathogenesis of AD by activating the Notch1 pathway to interfere with the immune response.
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