KL1333, a Novel NAD⁺ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts.

ABSTRACT: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), one of the most common maternally inherited mitochondrial diseases, is caused by mitochondrial DNA mutations that lead to mitochondrial dysfunction. Several treatment options exist, including supplementation with CoQ10, vitamins, and nutrients, but no treatment with proven efficacy is currently available. In this study, we investigated the effects of a novel NAD⁺ modulator, KL1333, in human fibroblasts derived from a human patient with MELAS. KL1333 is an orally available, small organic molecule that reacts with NAD(P)H:quinone oxidoreductase 1 (NQO1) as a substrate, resulting in increases in intracellular NAD⁺ levels via NADH oxidation. To elucidate the mechanism of action of KL1333,

SUBMITTER: Seo KS 

PROVIDER: S-EPMC6041391 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature