{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T02:47:06Z","timestamp":1783565226009,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Parkinson\u2019s 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 \u201cearly-warning system\u201d\u2014the mitochondrial retrograde signaling (MRS) pathway\u2014impairing the nucleus\u2019s ability to launch timely protective responses. This review repositions pterostilbene, a bioavailable dietary polyphenol, from a simple antioxidant to a \u201csignal fidelity enhancer\u201d 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\u2019s intrinsic capacity for self-maintenance and resilience.<\/jats:p>","DOI":"10.3389\/fnagi.2025.1692777","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T06:34:33Z","timestamp":1765521273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pterostilbene restores mitochondrial retrograde signaling to activate protective stress responses in Parkinson\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Fanshuai","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinna","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.08.23.24312501","article-title":"Randomized crossover clinical trial of nicotinamide riboside and coenzyme Q10 on metabolic health and mitochondrial bioenergetics in CKD","author":"Ahmadi","year":"2024","journal-title":"medRxiv"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.mito.2023.05.007","article-title":"Mitochondrial dysfunction and oxidative stress in Alzheimer's disease, and Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis -an updated review","volume":"71","author":"Alqahtani","year":"2023","journal-title":"Mitochondrion"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1002\/ana.27202","article-title":"Nigral Neuroinflammation and dopaminergic neurons in Parkinson's disease and atypical Parkinsonisms","volume":"97","author":"Backman","year":"2025","journal-title":"Ann. 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