ArticleNature medicine2012
TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 202 citations in OpenAlex.
- Article
- Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.Nature communications · 2026Article
- Temperature and intrinsic CaNature structural & molecular biology · 2026Article
- Potent Anthranilic Anilide-Based TRPM4 Channel Inhibitors Identified by a Structure-Activity Relationship Study.Journal of medicinal chemistry · 2026Article
- Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.bioRxiv : the preprint server for biology · 2026Article
- A GDF-15-GFRAL axis controls autoimmune T cell responses during neuroinflammation.Nature immunology · 2026Article
- Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions.CNS neuroscience & therapeutics · 2025Review
- The TRP channels serving as chemical-to-electrical signal converter.Physiological reviews · 2025Review
- Development and in vitro characterization of humanized antibodies for blocking human TRPM4 channel.Scientific reports · 2025Article
- TRP Channels in Excitotoxicity.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- ROS-regulated SUR1-TRPM4 drives persistent activation of NLRP3 inflammasome in microglia after whole-brain radiation.Acta neuropathologica communications · 2025Article
- Identification and development of TRPM4 antagonists to counteract neuronal excitotoxicity.iScience · 2024Article
- Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.International journal of molecular sciences · 2024Review
- Advancements in Targeting Ion Channels for the Treatment of Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024Review
- Roles of TRP and PIEZO receptors in autoimmune diseases.Expert reviews in molecular medicine · 2024Review
- Transient Receptor Potential Channels in the Healthy and Diseased Blood-Brain Barrier.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Review
- TRPM channels in health and disease.Nature reviews. Nephrology · 2024Review
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
- Neuroprotective Effects of Sinomenine on Experimental Autoimmune Encephalomyelitis via Anti-Inflammatory and Nrf2-Dependent Anti-Oxidative Stress Activity.Neuromolecular medicine · 2023Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In multiple sclerosis, an inflammatory disease of the central nervous system (CNS), axonal and neuronal loss are major causes for irreversible neurological disability. However, which molecules contribute to axonal and neuronal injury under inflammatory conditions remains largely unknown. Here we show that the transient receptor potential melastatin 4 (TRPM4) cation channel is crucial in this process. TRPM4 is expressed in mouse and human neuronal somata, but it is also expressed in axons in inflammatory CNS lesions in experimental autoimmune encephalomyelitis (EAE) in mice and in human multiple sclerosis tissue. Deficiency or pharmacological inhibition of TRPM4 using the antidiabetic drug glibenclamide resulted in reduced axonal and neuronal degeneration and attenuated clinical disease scores in EAE, but this occurred without altering EAE-relevant immune function. Furthermore, Trpm4(-/-) mouse neurons were protected against inflammatory effector mechanisms such as excitotoxic stress and energy deficiency in vitro. Electrophysiological recordings revealed TRPM4-dependent neuronal ion influx and oncotic cell swelling upon excitotoxic stimulation. Therefore, interference with TRPM4 could translate into a new neuroprotective treatment strategy.
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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.