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Nrf2 Activators in Parkinson's Disease: Modulating Mitophagy and Regulating Cuproptosis
Junjing Xu1, Jiawei Xiang1, Yong Zhang1
1Department of Histology and Embryology, School of Medicine, Shaoxing University, Shaoxing, 312000, Zhejiang, China.
Molecular Neurobiology
|July 2, 2026
Summary
Nuclear factor erythroid 2-related factor 2 (Nrf2) activators show promise for treating Parkinson's disease (PD). By targeting Nrf2, these therapies can reduce neuronal damage and restore cellular balance, offering a new therapeutic avenue for PD management.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Parkinson's disease (PD) involves the loss of dopaminergic neurons, driven by oxidative stress, neuroinflammation, cuproptosis, and mitochondrial dysfunction.
- Nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of cellular defense, is compromised in PD.
- Nrf2 activators are emerging as potential therapeutic agents for PD.
Purpose of the Study:
- To review the mechanisms by which Nrf2 activators modulate biological processes relevant to PD.
- To synthesize preclinical and early clinical findings on Nrf2-targeted therapies for PD.
- To identify challenges and future directions in Nrf2-based PD treatment.
Main Methods:
- Systematic review of literature on Nrf2 signaling in PD.
- Critical appraisal of preclinical and early clinical data for Nrf2 activators.
- Analysis of molecular pathways regulated by Nrf2.
Main Results:
- Nrf2 activators promote mitophagy, clearing damaged mitochondria and restoring metabolic homeostasis.
- Activation of Nrf2 suppresses copper accumulation and lipid peroxidation, inhibiting neuronal cuproptosis.
- Evidence suggests Nrf2 activators can mitigate key pathological cascades in PD.
Conclusions:
- Targeting the Nrf2 pathway offers a promising integrative therapeutic strategy for Parkinson's disease.
- Nrf2 activators demonstrate potential in addressing multiple facets of PD pathogenesis.
- Further research and clinical investigation are warranted to fully realize the therapeutic potential of Nrf2-based strategies for PD.
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