ArticleCell research2013
ALDH2 protects against stroke by clearing 4-HNE.
Article in Cell research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
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Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- Association Study and Meta-Analysis of Polymorphisms and Blood mRNA Expression of the ALDH2 Gene in Patients with Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Pooled it
- Far-infrared irradiation restores mitochondrial dynamics to ameliorate ischemic stroke.Neural regeneration research · 2026Article
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- VMAT-DAT-Dopamine Regulatory System Involved in the Protective Effect of 3-n-Butylphthalide Against Ischemic Stroke.CNS neuroscience & therapeutics · 2026Article
- Ferroptosis-related stress during aging and its relevance to disease.GeroScience · 2026Review
- Evaluation of the Nrf2-Keap1 Pathway in Patients with Acute Cerebral Ischemic Disease.Medicina (Kaunas, Lithuania) · 2026Article
- Alcohol Interaction and ALDH2: Missing Links in EMPHASIS.Cerebrovascular diseases (Basel, Switzerland) · 2026Article
- The Activation of Aldehyde Dehydrogenase 2 (ALDH2) by Alda-1 and Flurbiprofen as a Common Mechanism to Reduce Alcohol Intake in Rats.International journal of molecular sciences · 2026Article
- Oxeiptosis - potential in cancer treatment?Expert reviews in molecular medicine · 2026Review
- Increased susceptibility to 4-HNE-induced toxicity and impaired development in a model of ALDH4A1-deficient pediatric epilepsy carrying the S352L variant.Communications biology · 2026Article
- Early hypoxia-induced secretome remodeling reveals adaptive mechanisms and biomarkers of blood-brain barrier dysfunction in ischemic stroke.Molecular brain · 2026Article
- Genetic and epigenetic architectures of stroke: Insights from GWAS to precision medicine.Neurochemistry international · 2025Review
- Design, Synthesis, and Study of Protective Activity Against Stroke for Novel Water-Soluble Aldehyde Dehydrogenase 2 Activators.Molecules (Basel, Switzerland) · 2025Article
- ALDH2 Attenuates Blood-Brain Barrier Injury Induced by Cerebral Ischemia/Reperfusion via Alleviating ROS/NLRP3 Inflammasome Axis.Neurochemical research · 2025Article
- Neuroprotective effect of riboflavin kinase on cerebral ischemia injury in rats.Molecular medicine (Cambridge, Mass.) · 2025Article
- The Dopamine Transporter Is a New Target for Ischemic Stroke.CNS neuroscience & therapeutics · 2024Article
- Activation of mitochondrial aldehyde dehydrogenase 2 promotes hair growth in human hair follicles.Journal of advanced research · 2024Article
- A mitochondrial-targeted activity-based sensing probe for ratiometric imaging of formaldehyde reveals key regulators of the mitochondrial one-carbon pool.Chemical science · 2024Article
- Mitochondrial Aldehyde Dehydrogenase 2 (ALDH2) Protects against Binge Alcohol-Mediated Gut and Brain Injury.Cells · 2024Article
- Ischemic Brain Injury: Involvement of Lipids in the Pathophysiology of Stroke and Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2024Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that metabolizes ethanol and toxic aldehydes such as 4-hydroxy-2-nonenal (4-HNE). Using an unbiased proteomic search, we identified ALDH2 deficiency in stroke-prone spontaneously hypertensive rats (SHR-SP) as compared with spontaneously hypertensive rats (SHR). We concluded the causative role of ALDH2 deficiency in neuronal injury as overexpression or activation of ALDH2 conferred neuroprotection by clearing 4-HNE in in vitro studies. Further, ALDH2-knockdown rats revealed the absence of neuroprotective effects of PKCε. Moderate ethanol administration that is known to exert protection against stroke was shown to enhance the detoxification of 4-HNE, and to protect against ischemic cerebral injury through the PKCε-ALDH2 pathway. In SHR-SP, serum 4-HNE level was persistently elevated and correlated inversely with the lifespan. The role of 4-HNE in stroke in humans was also suggested by persistent elevation of its plasma levels for at least 6 months after stroke. Lastly, we observed that 21 of 1 242 subjects followed for 8 years who developed stroke had higher initial plasma 4-HNE levels than those who did not develop stroke. These findings suggest that activation of the ALDH2 pathway may serve as a useful index in the identification of stroke-prone subjects, and the ALDH2 pathway may be a potential target of therapeutic intervention in stroke.
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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.