Neurological diseases have a close relationship to excessive reactive oxygen species (ROS). Neuroglobin (Ngb), an intrinsic protective factor, protected cells from hypoxic/ischemic injury. In the present, we reported a novel neuroprotective manganese porphyrin reconstituted metal protein, Mn-TAT PTD-Ngb, consisting of a HIV Tat protein transduction domain sequence (TAT PTD) attached to the N-terminal of apo-Ngb. Mn-TAT PTD-Ngb had a stronger ROS scavenging ability than that of TAT PTD-Ngb, and reduced intracellular ROS production and restored the function of the mitochondria and inhibited the mitochondria-dependent apoptosis. Besides, Mn-TAT PTD-Ngb activated the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway, which up-regulated the expression of nuclear factor E2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT). The results showed that the redox chemistry of Mn-TAT PTD-Ngb and redox regulation of multiple signaling pathways attenuated the oxidative injury.
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