Potential Effects of Nrf2 in Exercise Intervention of Neurotoxicity Caused by Methamphetamine Oxidative Stress

Abstract

Methamphetamine can cause oxidative stress-centered lipid peroxidation, endoplasmic reticulum stress, mitochondrial dysfunction, excitatory neurotoxicity, and neuroinflammation and ultimately lead to nerve cell apoptosis, abnormal glial cell activation, and dysfunction of blood-brain barrier. Protecting nerve cells from oxidative destroy is a hopeful strategy for treating METH use disorder. Nrf2 is a major transcriptional regulator that activates the antioxidant, anti-inflammatory, and cell-protective gene expression through endogenous pathways that maintains cell REDOX homeostasis and is conducive to the survival of neurons. The Nrf2-mediated endogenous antioxidant pathway can also prevent neurodegenerative effects and functional defects caused by METH oxidative stress. Moderate exercise activates this endogenous antioxidant system, which involves in many diseases, including neurodegenerative diseases. Based on evidence from existing literature, we argue that appropriate exercise can play an endogenous antioxidant regulatory role in the Nrf2 signaling pathway to reduce a number of issues caused by METH-induced oxidative stress. However, more experimental evidence is needed to support this idea. In addition, further exploration is necessary about the different effects of various parameters of exercise intervention (such as exercise mode, time, and intensity) on the Nrf2 signaling pathway intervention. Whether there are synergistic effects between exercise and plant-derived Nrf2 activators is worth further investigation.