An unrecognized mechanism of neuroprotection by microglial TIA1-mediated stress granules to prevent neuroinflammation and demyelination in experimental autoimmune encephalomyelitis mice through sequestering ApoE mRNA.

-induced stress, TIA1 deficiency in BV2 cells and primary cultured microglia resulted in both enhanced phagocytic capacity and a pro-inflammatory phenotypic shift. Mechanistically, upon to stresses, microglial TIA1-mediated SGs formation was enhanced, leading to sequester ApoE mRNA into SGs to reduce ApoE expression, which in turn prevented excessive activation of microglia and inhibited demyelination in EAE mice. These findings uncover a previously unrecognized neuroprotective mechanism wherein TIA1-mediated SGs in microglia dynamically restrain neuroinflammation via post-transcriptional control of ApoE, revealing a new therapeutic avenue for MS.