The Alzheimer's disease drug candidate J147 decreases blood plasma fatty acid levels via modulation of AMPK/ACC1 signaling in the liver.

ABSTRACT: J147 is a novel drug candidate developed to treat neurological dysfunction. Numerous studies have demonstrated the beneficial effects of J147 in cellular and animal models of disease which has led to the transitioning of the compound into human clinical trials. However, no biomarkers for its target engagement have been identified. Here, we determined if specific metabolites in the plasma could be indicative of J147's activity in vivo. Plasma lipidomics data from three independent rodent studies were assessed along with liver lipidomics data from one of the studies. J147 consistently reduced plasma free fatty acid (FFA) levels across the independent studies. Decreased FFA levels were also found in the livers of J147-treated mice that correlated well with those in the plasma. These changes i

SUBMITTER: Kepchia D 

PROVIDER: S-EPMC8854339 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature