Numb-Ifi204 inhibits microglial activation and the hippocampal inflammation induced by LPS

We uncover a novel role for Numb in regulating microglial activation and highlight its interaction with Ifi204 in the LPS-induced TLR4 signaling pathway. We demonstrate that Numb promotes the autophagic degradation of Ifi204, thereby inhibiting the TLR4 signaling pathway and reducing excessive inflammatory responses in microglia.

Furthermore, our findings show that Numb-mediated inhibition of microglial inflammation protects hippocampal neurons from synaptic damage, morphological abnormalities, and apoptosis.