ArticleAging cell2017
Homocysteine modulates 5-lipoxygenase expression level via DNA methylation.
Article in Aging cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer's Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial.The journal of prevention of Alzheimer's diseaseTrial
- Impact of Vitamin B12, Folate and Homocysteine in Modulating Cognitive Functions and the Brain's White Matter Hyperintensity in Alzheimer's Disease.Annals of neurosciences · 2026Article
- Impact of Alterations in Homocysteine, Asymmetric Dimethylarginine and Vitamins-Related Pathways in Some Neurodegenerative Diseases: A Narrative Review.International journal of molecular sciences · 2025Review
- Article
- The Role of DNA Methylation in Stroke Recovery.International journal of molecular sciences · 2022Review
- Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids.Life research · 2022Article
- miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia.Acta biochimica et biophysica Sinica · 2022Article
- miR-195-3p alleviates homocysteine-mediated atherosclerosis by targeting IL-31 through its epigenetics modifications.Aging cell · 2021Article
- Dysregulation of the Retromer Complex System in Down Syndrome.Annals of neurology · 2020Article
- Abnormal Homocysteine Metabolism: An Insight of Alzheimer's Disease from DNA Methylation.Behavioural neurology · 2020Review
- Nitrative Stress-Related Autophagic Insufficiency Participates in Hyperhomocysteinemia-Induced Renal Aging.Oxidative medicine and cellular longevity · 2020Article
- Article
- Dysregulation of Epigenetic Mechanisms of Gene Expression in the Pathologies of Hyperhomocysteinemia.International journal of molecular sciences · 2019Review
- The Non-Essential Amino Acid Cysteine Becomes Essential for Tumor Proliferation and Survival.Cancers · 2019Review
- Emodin Rescued Hyperhomocysteinemia-Induced Dementia and Alzheimer's Disease-Like Features in Rats.The international journal of neuropsychopharmacology · 2019Article
- Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism.International journal of molecular sciences · 2018Review
- Association of Induced Hyperhomocysteinemia with Alzheimer's Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury.Neurochemical research · 2018Article
- Dissecting the Role of 5-Lipoxygenase in the Homocysteine-Induced Alzheimer's Disease Pathology.Journal of Alzheimer's disease : JAD · 2018Review
- Cystathionine β-synthase deficiency: Of mice and men.Molecular genetics and metabolism · 2017Review
- Genetic absence of ALOX5 protects from homocysteine-induced memory impairment, tau phosphorylation and synaptic pathology.Human molecular genetics · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Elevated levels of homocysteinemia (Hcy), a risk factor for late-onset Alzheimer's disease (AD), have been associated with changes in cell methylation. Alzheimer's disease is characterized by an upregulation of the 5-lipoxygenase (5LO), whose promoter is regulated by methylation. However, whether Hcy activates 5LO enzymatic pathway by influencing the methylation status of its promoter remains unknown. Brains from mice with high Hcy were assessed for the 5LO pathway and neuronal cells exposed to Hcy implemented to study the mechanism(s) regulating 5LO expression levels and the effect on amyloid β formation. Diet- and genetically induced high Hcy resulted in 5LO protein and mRNA upregulation, which was associated with a significant increase of the S-adenosylhomocysteine (SAH)/S-adenosylmethionine ratio, and reduced DNA methyltrasferases and hypomethylation of 5-lipoxygenase DNA. In vitro studies confirmed these results and demonstrated that the mechanism involved in the Hcy-dependent 5LO activation and amyloid β formation is DNA hypomethylation secondary to the elevated levels of SAH. Taken together these findings represent the first demonstration that Hcy directly influences 5LO expression levels and establish a previously unknown cross talk between these two pathways, which is highly relevant for AD pathogenesis. The discovery of such a novel link not only provides new mechanistic insights in the neurobiology of Hcy, but most importantly new therapeutic opportunities for the individuals bearing this risk factor for the disease.
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