Nicotinamide mononucleotide combined with PJ-34 protects microglial cells from lipopolysaccharide-induced mitochondrial impairment through NMNAT3-PARP1 axis.

ABSTRACT: Lipopolysaccharide (LPS) is known to induce cell injury and mitochondrial dysfunction, which are pivotal in neuroinflammation and related disorders. Recent studies have demonstrated the potential of nicotinamide mononucleotide (NMN) and poly(ADP-ribose) polymerase-1 (PARP1) inhibitors to enhance mitochondrial function. However, the underlying mechanisms have not been fully elucidated. This study investigates the impact of NMN in conjunction with PJ-34, a PARP1 inhibitor, on LPS-induced mitochondrial damage, focusing on nicotinamide mononucleotide adenylyl transferase 3 (NMNAT3) -PARP1 axis. The results showed that LPS treatment led to down-regulation of NMNAT3 (decreased 58.72% at 1 µM), up-regulation of PARP1 (enhanced 22.78% at 1 µM), thereby impairing mitophagy and mitochondrial functio

SUBMITTER: Li J 

PROVIDER: S-EPMC11884077 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature