Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism

Significance Human microglia, the resident immune cells of the brain, express only the neurotensin (NT) receptor-3/sortilin. NT significantly increases microglia synthesis and release of proinflammatory cytokine IL-1β and chemokine (C-X-C motif) ligand 8 (CXCL8), chemokine (C-C motif) ligand 2 (CCL2), and CCL5 via NTR3/sortilin. A soluble form of this receptor is secreted from stimulated microglia and is increased in the serum of children with autism spectrum disorders (ASD). These responses and the NT-stimulated increases in microglia numbers are mediated via mammalian target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) (mTOR) activation and are inhibitable by the natural flavonoids luteolin and methoxyluteolin.