ArticleHuman molecular genetics2011
ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington's disease.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 of them syntheses that pooled it.
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Who cites it
120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 230 citations in OpenAlex.
- The Neuroprotective Role of Fisetin in Different Neurological Diseases: a Systematic Review.Molecular neurobiology · 2023Pooled it
- Therapeutic benefits of flavonoids against neuroinflammation: a systematic review.Inflammopharmacology · 2022Pooled it
- Oxidative stress and inflammation in neurodegenerative disorders.Archives of toxicology · 2026Review
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in WI-38 replicative senescent cells.Cell death & disease · 2026Article
- Neuroprotective potential of resveratrol in Parkinson, Huntington, amyotrophic lateral sclerosis, and multiple sclerosis: a comprehensive review.Molecular biology reports · 2026Review
- Roles of MAPKs, Including Those Activated by BDNF/TrkB, and Their Contribution in Neurodegenerative Diseases.International journal of molecular sciences · 2026Review
- Epidermal growth factor receptor modulation for neural repair: Implications for neurodegenerative disease therapy.Frontiers in molecular neuroscience · 2026Review
- Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease.npj aging · 2025Review
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in senescent cells.Research square · 2025Article
- The Ubiquitin-Proteasome System in Brain Disorders: Pathogenic Pathways, Post-Translational Tweaks, and Therapeutic Frontiers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Resveratrol: A Natural Compound Targeting the PI3K/Akt/mTOR Pathway in Neurological Diseases.Molecular neurobiology · 2025Review
- Opposing roles for GSK3β and ERK1-dependent phosphorylation of huntingtin during neuronal dysfunction and cell death in Huntington's disease.Cell death & disease · 2025Article
- Fisetin: hormesis accounts for many of its chemoprotective effects.Biogerontology · 2025Review
- Mechanistic insights on the role of Nrf-2 signalling in Huntington's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Promising potential effects of resveratrol on oral and dental health maintenance: a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Recent Prospectives of Cellular Signaling Role for Mammary Gland Carcinogenesis.Anti-cancer agents in medicinal chemistry · 2025Review
- The flavonoid fisetin reduces multiple physiological risk factors for dementia.Neurochemistry international · 2024Review
- Effectiveness of Flavonoid-Rich Diet in Alleviating Symptoms of Neurodegenerative Diseases.Foods (Basel, Switzerland) · 2024Review
- CMS121 Partially Attenuates Disease Progression in Mouse Models of Huntington's Disease.Molecular neurobiology · 2024Article
- A clinical study and future prospects for bioactive compounds and semi-synthetic molecules in the therapies for Huntington's disease.Molecular neurobiology · 2024Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Huntington's disease (HD) is an inherited, progressive and ultimately fatal neurodegenerative disorder that is characterized by psychiatric, cognitive and motor symptoms. Among the pathways implicated in HD are those involving mitogen-activated protein kinase signaling and particularly the Ras-extracellular signal-regulated kinase (ERK) cascade. Studies in both cells and animal models suggest that ERK activation might provide a novel therapeutic target for the treatment of HD but compounds that specifically activate ERK are few. To test the hypothesis that pharmaceutical activation of ERK might be protective for HD, a polyphenol, fisetin, which was previously shown to activate the Ras-ERK cascade, was tested in three different models of HD: PC12 cells expressing mutant Httex1 under the control of an inducible promoter, Drosophila expressing mutant Httex1 and the R6/2 mouse model of HD. The results indicate that fisetin can reduce the impact of mutant huntingtin in each of these disease models. Prompted by this observation, we determined that the related polyphenol, resveratrol, also activates ERK and is protective in HD models. Notably, although more than a dozen small molecule inhibitors of ERK activation are in clinical trials, very few small molecule activators of ERK signaling are reported. Thus, fisetin, resveratrol and related compounds might be useful for the treatment of HD by virtue of their unique ability to activate ERK.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.