ArticleEMBO molecular medicine2020
Inhibiting MARSs reduces hyperhomocysteinemia-associated neural tube and congenital heart defects.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- N-Homocysteinylation of Cofilin-1 Aggravates Epileptic Pathophysiology via Disruption of Actin Dynamics.Neuroscience bulletin · 2026Article
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- Isoleucyl-tRNA synthetase 1 mutation impairs pulmonary surfactant homeostasis by disrupting alveolar macrophage function.Respiratory research · 2026Article
- Chiral methionine oxidation reagents reveal stereospecific proteome modifications.bioRxiv : the preprint server for biology · 2026Article
- Depletion of tryptophanyl-tRNA synthetase and tryptophan accumulation triggers p53-dependent apoptosis.Cell death discovery · 2025Article
- Glutamine signaling specifically activates c-Myc and Mcl-1 to facilitate cancer cell proliferation and survival.Protein & cell · 2025Article
- The tumor-promoting role of methionyl-tRNA synthetase 1 in ovarian cancer and its potential mechanisms.Medical oncology (Northwood, London, England) · 2025Article
- Fundamental origins of neural tube defects with a basis in genetics and nutrition.Experimental brain research · 2025Review
- Early Detection and Management of Cognitive Impairment in Parkinson's Disease: A Predictive Model Approach.Brain and behavior · 2025Article
- Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease.International journal of molecular sciences · 2025Review
- N-Homocysteinylation of HMGB1/2 Promotes Corpus Cavernosum Endothelial Senescence in Erectile Dysfunction.International journal of biological sciences · 2025Article
- High Homocysteine-Thiolactone Leads to Reduced MENIN Protein Expression and an Impaired DNA Damage Response: Implications for Neural Tube Defects.Molecular neurobiology · 2024Article
- CXCL16 promotes proliferation of head and neck squamous cell carcinoma by regulating GPX1-mediated antioxidant levels.Journal of Zhejiang University. Science. B · 2024Article
- Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer's Disease.International journal of molecular sciences · 2024Review
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- Changes in Oxidative Stress Markers in Pregnant Women of Advanced Maternal Age with Gestational Diabetes and Their Predictive Value for Neurodevelopmental Impact.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease.EMBO molecular medicine · 2023Article
- Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease.Cell reports. Medicine · 2023Article
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
Hyperhomocysteinemia is a common metabolic disorder that imposes major adverse health consequences. Reducing homocysteine levels, however, is not always effective against hyperhomocysteinemia-associated pathologies. Herein, we report the potential roles of methionyl-tRNA synthetase (MARS)-generated homocysteine signals in neural tube defects (NTDs) and congenital heart defects (CHDs). Increased copy numbers of MARS and/or MARS2 were detected in NTD and CHD patients. MARSs sense homocysteine and transmit its signal by inducing protein lysine (N)-homocysteinylation. Here, we identified hundreds of novel N-homocysteinylated proteins. N-homocysteinylation of superoxide dismutases (SOD1/2) provided new mechanistic insights for homocysteine-induced oxidative stress, apoptosis and Wnt signalling deregulation. Elevated MARS expression in developing and proliferating cells sensitizes them to the effects of homocysteine. Targeting MARSs using the homocysteine analogue acetyl homocysteine thioether (AHT) reversed MARS efficacy. AHT lowered NTD and CHD onsets in retinoic acid-induced and hyperhomocysteinemia-induced animal models without affecting homocysteine levels. We provide genetic and biochemical evidence to show that MARSs are previously overlooked genetic determinants and key pathological factors of hyperhomocysteinemia, and suggest that MARS inhibition represents an important medicinal approach for controlling hyperhomocysteinemia-associated diseases.
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Registered trials
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