Inhibiting 15-PGDH blocks blood-brain barrier deterioration and protects mice from Alzheimer's disease and traumatic brain injury.

ABSTRACT: Alzheimer's disease (AD) and traumatic brain injury (TBI) are currently untreatable neurodegenerative disorders afflicting millions of people worldwide. These conditions are pathologically related, and TBI is one of the greatest risk factors for AD. Although blood-brain barrier (BBB) disruption drives progression of both AD and TBI, strategies to preserve BBB integrity have been hindered by lack of actionable targets. Here, we identify 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme that catabolizes eicosanoids and other anti-inflammatory mediators, as a therapeutic candidate that protects the BBB. We demonstrate that 15-PGDH is enriched in BBB-associated myeloid cells and becomes markedly elevated in human and mouse models of AD and TBI, as well as aging, another major risk fac

SUBMITTER: Koh Y 

PROVIDER: S-EPMC12130856 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature