Antioxidants attenuate mitochondrial oxidative damage through the Nrf2 pathway: A promising therapeutic strategy for stroke

Abstract

Stroke represents one of the leading causes of disability and death worldwide.Reactive oxygen species overproduction-induced oxidative stress in mitochondria results in mitochondrial DNA damage, mitochondrial autophagy (mitophagy), inflammation, and apoptosis during the pathologic progression of stroke. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator that induces the transcription of a wide range of antioxidant genes to attenuate mitochondrial oxidative stress.Different antioxidative compounds, including polyphenols, mitochondrial antioxidants, triterpenoids, and others, have been shown to be able to activate Nrf2 and, thus, exert neuroprotective effects on stroke by ameliorating mitochondrial oxidative damage. In this review, we briefly discussed the role of mitochondrial oxidative stress in the pathophysiology of stroke and focused on the protective effects of antioxidative compounds through attenuating mitochondrial oxidative damage by activating Nrf2 in stroke. In conclusion, these antioxidants may represent novel therapeutic strategies against stroke.

Effects of Dityrosine on Lactic Acid Metabolism in Mice Gastrocnemius Muscle During Endurance Exercise via the Oxidative Stress-Induced Mitochondria Damage

“…Among these, the Nrf2/ARE signaling pathway has been recognized as one of the important mechanisms in the mitochondrial antioxidant system. 70 The ARE is situated in the promoter region of certain genes encoding antioxidant-related enzymes, including Gpx-1, Ho-1, and Nqo1. 71 Under normal conditions, Nrf2 binds to Kelchlike ECH-associated protein-1 (Keap1) and is associated with the actin cytoskeleton in the cytoplasm.…”

“…The process of alleviating damage caused by oxidative stress through the antioxidant system is a complex pathophysiological process, involving a series of molecular events and cellular signaling pathways. Among these, the Nrf2/ARE signaling pathway has been recognized as one of the important mechanisms in the mitochondrial antioxidant system . The ARE is situated in the promoter region of certain genes encoding antioxidant-related enzymes, including Gpx-1 , Ho-1 , and Nqo1 .…”