ArticleJournal of neurochemistry2019
Non-canonical activation of CREB mediates neuroprotection in a Caenorhabditis elegans model of excitotoxic necrosis.
Article in Journal of neurochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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.
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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
8 citing papers in PubMed, 9 citations in OpenAlex.
- AlteredeNeuro · 2026Article
- Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.Acta pharmacologica Sinica · 2025Review
- AlteredbioRxiv : the preprint server for biology · 2025Article
- Article
- New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity.Frontiers in molecular neuroscience · 2022Review
- Regulation of Social Stress and Neural Degeneration by Activity-Regulated Genes and Epigenetic Mechanisms in Dopaminergic Neurons.Molecular neurobiology · 2020Review
- Excitotoxicity: Still Hammering the Ischemic Brain in 2020.Frontiers in neuroscience · 2020Review
- More than anti-malarial agents: therapeutic potential of artemisinins in neurodegeneration.Neural regeneration research · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Excitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu-receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingly, signaling downstream of GluRs can also activate neuroprotective pathways. The strongest evidence involves activation of the transcription factor cAMP response element-binding protein (CREB), widely recognized for its importance in synaptic plasticity. Canonical views describe CREB as a phosphorylation-triggered transcription factor, where transcriptional activation involves CREB phosphorylation and association with CREB-binding protein. However, given CREB's ubiquitous cross-tissue expression, the multitude of cascades leading to CREB phosphorylation, and its ability to regulate thousands of genes, it remains unclear how CREB exerts closely tailored, differential neuroprotective responses in excitotoxicity. A non-canonical, alternative cascade for activation of CREB-mediated transcription involves the CREB co-factor cAMP-regulated transcriptional co-activator (CRTC), and may be independent of CREB phosphorylation. To identify cascades that activate CREB in excitotoxicity we used a Caenorhabditis elegans model of neurodegeneration by excitotoxic necrosis. We demonstrated that CREB's neuroprotective effect was conserved, and seemed most effective in neurons with moderate Glu exposure. We found that factors mediating canonical CREB activation were not involved. Instead, phosphorylation-independent CREB activation in nematode excitotoxic necrosis hinged on CRTC. CREB-mediated transcription that depends on CRTC, but not on CREB phosphorylation, might lead to expression of a specific subset of neuroprotective genes. Elucidating conserved mechanisms of excitotoxicity-specific CREB activation can help us focus on core neuroprotective programs in excitotoxicity. Cover Image for this issue: doi: 10.1111/jnc.14494.
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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 Socratic graph.