ArticleeLife2015
Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 97 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- The Role of ASIC1a in Inflammatory Immune Diseases: A Potential Therapeutic Target.Frontiers in pharmacology · 2022Pooled it
- ASIC1a as an integrating node in ischemic neurotoxicity: crosstalk with NMDAR and TRPM signaling.Pflugers Archiv : European journal of physiology · 2026Review
- Acid-sensing ion channels in ischemic stroke: amplifying and constraining neuronal injury in a phase-specific framework.Pflugers Archiv : European journal of physiology · 2026Review
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- The multifaceted role of ASICs channels into the nervous system and their potential use as a therapeutic target for neuro-disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Mitochondrial acid-sensing ion channel 1a deficiency induces mitochondrial dysfunction in pulmonary arterial smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- The acid-sensing ion channel 1a modulates anxiety- and depression-related behaviors via its influencing on the activity of corticotropin-releasing hormone-expressing neurons in the hypothalamic paraventricular nucleus in male mice.Translational psychiatry · 2026Article
- Web of Potentials: Neuroactive Components of Spider Venom and Their Emerging Pharmacologic Applications in Neurologic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Endogenous forms of ATP-ATPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nonionotropic action of an acid-sensing ion channel inhibits leukemogenesis in the acidic bone marrow niche.The Journal of clinical investigation · 2025Article
- Molecular Mechanism of MLC 901 in Acute Ischemic Stroke: A Review.Stroke research and treatment · 2025Review
- Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors.Nature communications · 2024Article
- Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond.Protein & cell · 2024Review
- ASIC1/RIP1 accelerates atherosclerosis via disrupting lipophagy.Journal of advanced research · 2024Article
- Dynamic conformational changes of acid-sensing ion channels in different desensitizing conditions.Biophysical journal · 2024Article
- Article
- Functional expression of the proton sensors ASIC1a, TMEM206, and OGR1 together with BKPflugers Archiv : European journal of physiology · 2024Article
- Progress on functions of intracellular domainZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Hi1a Improves Sensorimotor Deficit following Endothelin-1-Induced Stroke in Rats but Does Not Improve Functional Outcomes following Filament-Induced Stroke in Mice.ACS pharmacology & translational science · 2024Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Acidotoxicity is common among neurological disorders, such as ischemic stroke. Traditionally, Ca(2+) influx via homomeric acid-sensing ion channel 1a (ASIC1a) was considered to be the leading cause of ischemic acidotoxicity. Here we show that extracellular protons trigger a novel form of neuronal necroptosis via ASIC1a, but independent of its ion-conducting function. We identified serine/threonine kinase receptor interaction protein 1 (RIP1) as a critical component of this form of neuronal necroptosis. Acid stimulation recruits RIP1 to the ASIC1a C-terminus, causing RIP1 phosphorylation and subsequent neuronal death. In a mouse model of focal ischemia, middle cerebral artery occlusion causes ASIC1a-RIP1 association and RIP1 phosphorylation in affected brain areas. Deletion of the Asic1a gene significantly prevents RIP1 phosphorylation and brain damage, suggesting ASIC1a-mediated RIP1 activation has an important role in ischemic neuronal injury. Our findings indicate that extracellular protons function as a novel endogenous ligand that triggers neuronal necroptosis during ischemia via ASIC1a independent of its channel function.
Indexed as
Identifiers
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.