MINI REVIEW article
Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
This article is part of the Research TopicMechanisms and Novel Therapeutic Targets and Approaches for Mitochondrial Dysfunction in Neurological and Cardiovascular DiseasesView all 8 articles
Pterostilbene Restores Mitochondrial Retrograde Signaling to Activate Protective Stress Responses in Parkinson's Disease
Provisionally accepted
- 1The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China
- 2Changchun University of Chinese Medicine, Changchun, China
- 3Xi'an Jiaotong University Health Science Center, Xi'an, China
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Parkinson's disease (PD) is the selective demise of dopaminergic neurons in the substantia nigra. Conventional neuroprotective strategies based on exogenous antioxidants have shown minimal clinical efficacy. Emerging evidence suggests that neuronal loss in PD may stem not only from direct mitochondrial damage but, more critically, from the failure of an intrinsic "early-warning system"—the mitochondrial retrograde signaling (MRS) pathway—impairing the nucleus's ability to launch timely protective responses. This review repositions pterostilbene, a bioavailable dietary polyphenol, from a simple antioxidant to a "signal fidelity enhancer" that supports mitochondria-to-nucleus communication. By stabilizing mitochondrial function and modulating stress-sensing pathways, pterostilbene may restore MRS integrity and promote activation of endogenous defense mechanisms such as the mitochondrial unfolded protein response (UPRmt). The article advocates a paradigm shift in nutritional neuroprotection: from passive supplementation toward reinforcing the neuron's intrinsic capacity for self-maintenance and resilience.
Keywords: pterostilbene, Parkinson's disease, Mitochondrial retrograde signaling, DopaminergicNeurons, Neuroprotection, Polyphenols, cellular resilience
Received: 27 Aug 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Zeng, Li, Yang, Lu and Xinna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wang Xinna
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