Epitranscriptomic reader YTHDF2 regulates SEK1(MAP2K4)-JNK-cJUN inflammatory signaling in astrocytes during neurotoxic stress.

ABSTRACT: As the most abundant glial cells in the central nervous system (CNS), astrocytes dynamically respond to neurotoxic stress, however, the key molecular regulators controlling the inflammatory status of these sentinels during neurotoxic stress are many and complex. Herein, we demonstrate that the m6A epitranscriptomic mRNA modification tightly regulates the pro-inflammatory functions of astrocytes. Specifically, the astrocytic neurotoxic stressor, manganese (Mn), downregulated the m6A reader YTHDF2 in human and mouse astrocyte cultures and in the mouse brain. Functionally, YTHDF2 knockdown augmented, while its overexpression dampened, the neurotoxic stress-induced proinflammatory response, suggesting YTHDF2 serves as a key upstream regulator of inflammatory responses in astrocytes. Mechanisti

SUBMITTER: Malovic E 

PROVIDER: S-EPMC11382029 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature