Bioactive Nanoenzyme Reverses Oxidative Damage and Endoplasmic Reticulum Stress in Neurons under Ischemic Stroke

ACS Nano. 2022 Jan 25;16(1):431-452. doi: 10.1021/acsnano.1c07205. Epub 2021 Dec 27.

Abstract

Designing translational antioxidative agents that could scavenge free radicals produced during reperfusion in brain ischemia stroke and alleviate neurologic damage is the main objective for ischemic stroke treatment. Herein, we explored and simply synthesized a biomimic and translational Mn3O4 nanoenzyme (HSA-Mn3O4) to constrain ischemic stroke reperfusion-induced nervous system injury. This nanosystem exhibits reduced levels of inflammation and prolonged circulation time and potent ROS scavenging activities. As expected, HSA-Mn3O4 effectively inhibits oxygen and glucose deprivation-mediated cell apoptosis and endoplasmic reticulum stress and demonstrates neuroprotective capacity against ischemic stroke and reperfusion injury of brain tissue. Furthermore, HSA-Mn3O4 effectively releases Mn ions and promotes the increase of superoxide dismutase 2 activity. Therefore, HSA-Mn3O4 inhibits brain tissue damage by restraining cell apoptosis and endoplasmic reticulum stress in vivo. Taken together, this study not only sheds light on design of biomimic and translational nanomedicine but also reveals the neuroprotective action mechanisms against ischemic stroke and reperfusion injury.

Keywords: endoplasmic reticulum stress; ischemic stroke; nanoenzyme; oxidative damage; superoxide dismutase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Apoptosis
  • Brain Ischemia* / drug therapy
  • Endoplasmic Reticulum Stress
  • Humans
  • Ischemic Stroke* / drug therapy
  • Neurons
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Oxidative Stress
  • Reperfusion Injury* / drug therapy
  • Stroke* / drug therapy

Substances

  • Neuroprotective Agents
  • Antioxidants