Redox Regulation and Mitochondrial Neuroprotection in Ischemic Stroke: The Emerging Role of DJ-1 (PARK7).

Abstract

Ischemic stroke remains a leading cause of global mortality and long-term disability, driven largely by oxidative stress, mitochondrial dysfunction, and inflammatory cascades. DJ-1 (PARK7), a redox-sensitive protein originally implicated in Parkinson's disease, has emerged as a critical neuroprotective regulator in cerebral ischemia. Oxidation of its cysteine-106 residue enables DJ-1 to stabilize mitochondrial function, suppress reactive oxygen species, and activate Nrf2-dependent antioxidant defenses. DJ-1 deficiency markedly exacerbates infarct size and neuronal vulnerability, whereas its activation confers robust neuroprotection. This review highlights DJ-1 as a promising redox-responsive therapeutic target for limiting ischemic brain injury.

Key Findings

• DJ-1 (PARK7) is a redox-sensitive protein that plays a critical neuroprotective role in ischemic stroke by stabilizing mitochondrial function and suppressing reactive oxygen species.
• Oxidation of cysteine-106 on DJ-1 activates Nrf2-dependent antioxidant defenses.
• DJ-1 deficiency increases infarct size and neuronal vulnerability, while activation of DJ-1 confers neuroprotection.

Clinical Significance

Citation

Ganamurali Nila, Ravikumar Alexander, Saravanan Sandhyaet al.. Redox Regulation and Mitochondrial Neuroprotection in Ischemic Stroke: The Emerging Role of DJ-1 (PARK7). Comprehensive Physiology. 2026-Jun.