These findings suggest a unique mechanism for the regulation of microglial autophagy and point to the PI3K-FOXO3 pathway as a potential therapeutic target to regulate microglial function in brain disorders.
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) is a developmental brain disorder characterized by megalencephaly and bilateral perisylvian polymicrogyria due to defects in genes of the PI3K-AKT pathway.
Postzygotic somatic mutations activating the phosphatidylinositol-4,5-bisphosphate-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway are found in a wide range of brain diseases, including FMCDs.