Role of prostacyclin signaling in endothelial production of soluble amyloid precursor protein-α in cerebral microvessels.

ABSTRACT: We tested hypothesis that activation of the prostacyclin (PGI₂) receptor (IP receptor) signaling pathway in cerebral microvessels plays an important role in the metabolism of amyloid precursor protein (APP). In human brain microvascular endothelial cells activation of IP receptor with the stable analogue of PGI₂, iloprost, stimulated expression of amyloid precursor protein and a disintegrin and metalloprotease 10 (ADAM10), resulting in an increased production of the neuroprotective and anticoagulant molecule, soluble APPα (sAPPα). Selective agonist of IP receptor, cicaprost, and adenylyl cyclase activator, forskolin, also enhanced expression of amyloid precursor protein and ADAM10. Notably, in cerebral microvessels of IP receptor knockout mice, protein levels of APP a

SUBMITTER: He T 

PROVIDER: S-EPMC5363732 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature