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

Authors: Arti Patel, Irene Tsilioni, Susan E. Leeman, Theoharis C. Theoharides - Proceedings of the National Academy of Sciences, PNAS 2016 cited by 120

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 rapamycin (mTOR) activation and are inhibitable by the natural flavonoids luteolin and methoxyluteolin.