ArticleJournal of neurochemistry2009
Homocysteine-NMDA receptor-mediated activation of extracellular signal-regulated kinase leads to neuronal cell death.
Article in Journal of neurochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Homocysteine and cognitive function in depression: a systematic review and meta-analysis.Frontiers in psychiatry · 2026Pooled it
- Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy: Metabolomics insights from the VITACOG trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Role of Folate Metabolism in Neurodegenerative Diseases: Insight from Experimental and Clinical Studies.Current nutrition reports · 2026Review
- Stroke in persistent chronic kidney disease condition alters innate-immunity to escalate mitochondrial dysfunction and aging.npj aging · 2026Article
- Association Between Homocysteine, Vitamin B12, Folate and Migraine: An Updated Systematic Review and Meta-Analysis.Brain sciences · 2026Review
- Neurotoxicity mechanisms and clinical implications of six common recreational drugs.Frontiers in pharmacology · 2025Review
- N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.Molecular neurobiology · 2025Article
- Impairment of neuronal tyrosine phosphatase STEP worsens post-ischemic inflammation and brain injury under hypertensive condition.Journal of neuroinflammation · 2024Article
- Central Causation of Autism/ASDs via Excessive [CaBrain sciences · 2024Review
- Targeting Reactive Astrocytes in Vascular Dementia: Investigation of Neuronal-Astrocyte-Vascular Interactions.Neuroscience insights · 2024Article
- Susceptibility to preoperative seizures in glioma patients with elevated homocysteine levels.Epilepsia open · 2023Article
- Folate and Its Significance in Depressive Disorders and Suicidality: A Comprehensive Narrative Review.Nutrients · 2023Review
- Homocysteine May Decrease Glucose Uptake and Alter the Akt/GSK3β/GLUT1 Signaling Pathway in Hippocampal Slices: Neuroprotective Effects of Rivastigmine and Ibuprofen.Molecular neurobiology · 2023Article
- Article
- Article
- Genetic Markers for Thrombophilia and Cardiovascular Disease Associated with Multiple Sclerosis.Biomedicines · 2022Article
- Hyperhomocysteinemia Induces Rat Memory Impairment Via Injuring Hippocampal CA3 Neurons and Downregulating cAMP Response Element-Binding Protein (CREB) Phosphorylation.Neurochemical research · 2022Article
- Review
- Hyperhomocysteinemia is a risk factor for postoperative ischemia in adult patients with moyamoya disease.Neurosurgical review · 2021Article
- Homocysteine and Age-Related Central Nervous System Diseases: Role of Inflammation.International journal of molecular sciences · 2021Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Hyperhomocysteinemia is an independent risk factor for stroke and neurological abnormalities. However, the underlying cellular mechanisms by which elevated homocysteine can promote neuronal death is not clear. In the present study we have examined the role of NMDA receptor-mediated activation of the extracellular signal-regulated kinase-mitogen-activated protein (ERK-MAP) kinase pathway in homocysteine-dependent neurotoxicity. The study demonstrates that in neurons l-homocysteine-induced cell death was mediated through activation of NMDA receptors. The study also shows that homocysteine-dependent NMDA receptor stimulation and resultant Ca2+ influx leads to rapid and sustained phosphorylation of ERK-MAP kinase. Inhibition of ERK phosphorylation attenuates homocysteine-mediated neuronal cell death thereby demonstrating that activation of ERK-MAP kinase signaling pathway is an intermediate step that couples homocysteine-mediated NMDA receptor stimulation to neuronal death. The findings also show that cAMP response-element binding protein (CREB), a pro-survival transcription factor and a downstream target of ERK, is only transiently activated following homocysteine exposure. The sustained activation of ERK but a transient activation of CREB together suggest that exposure to homocysteine initiates a feedback loop that shuts off CREB signaling without affecting ERK phosphorylation and thereby facilitates homocysteine-mediated neurotoxicity.
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What OpenQuestion holds
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.