Mn-TAT PTD-Ngb ameliorates inflammation through the elimination of damaged mitochondria and the activation of Nrf2-antioxidant signaling pathway.

Inflammation, mitochondrial dysfunction and oxidative stress are closely associated with neurological diseases. In this study, Mn-TAT PTD-Ngb, a novel artificial recombinant protein, exerted inhibitory effects on the inflammatory response and inflammasome activation. During the lipopolysaccharide (LPS)-induced inflammatory response, Mn-TAT PTD-Ngb suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and the release of proinflammatory cytokines and attenuated the phosphorylation of mitogen-activated protein kinase (MAPK). Furthermore, the recombinant protein blocked reactive oxygen species (ROS) production, abated mitochondrial dysfunction and significantly suppressed the assembly of the inflammasome, which led to the overproduction of proinflammatory cytokines IL-1β and IL-18. Mn-TAT PTD-Ngb increased the level of nuclear factor-erythroid 2 -related factor 2 (Nrf2), which protected against oxidative stress and improved pyroptosis. Mn-TAT PTD-Ngb might be a promising drug for curing neurological diseases.