ArticleProceedings of the National Academy of Sciences of the United States of America2018
Selection of an ASIC1a-blocking combinatorial antibody that protects cells from ischemic death.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Acid-sensing ion channels in ischemic stroke: amplifying and constraining neuronal injury in a phase-specific framework.Pflugers Archiv : European journal of physiology · 2026Review
- Assessing Computational Strategies for the Evaluation of Antibody Binding Affinities.Journal of chemical theory and computation · 2025Article
- The secreted protein PCYOX1L controls the surface expression of acid-sensing ion channel 1a.Science advances · 2025Article
- A dangerous liaison: Spreading depolarization and tissue acidification in cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Review
- Selective blockade of acid-sensing ion channel 1a can provide substantial hippocampal neuroprotection.Frontiers in cell and developmental biology · 2025Article
- Review
- Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Selection of Leptin Surrogates by a General Phenotypic Screening Method for Receptor Agonists.Biomolecules · 2024Article
- Glymphatic and lymphatic communication with systemic responses during physiological and pathological conditions in the central nervous system.Communications biology · 2024Review
- Methods for Engineering Binders to Multi-Pass Membrane Proteins.Bioengineering (Basel, Switzerland) · 2023Review
- Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins.iScience · 2023Article
- The role of acid sensing ion channels in the cardiovascular function.Frontiers in physiology · 2023Review
- Advances in Antibody-Based Therapeutics for Cerebral Ischemia.Pharmaceutics · 2022Review
- Segmental Upregulation of ASIC1 Channels in the Formalin Acute Pain Mouse Model.Pharmaceuticals (Basel, Switzerland) · 2022Article
- In Silico Maturation of a Nanomolar Antibody against the Human CXCR2.Biomolecules · 2022Article
- Therapeutic antibodies - natural and pathological barriers and strategies to overcome them.Pharmacology & therapeutics · 2022Review
- Article
- Commentary: Pharmacological Validation of ASIC1a as a Druggable Target for Neuroprotection in Cerebral Ischemia Using an Intravenously Available Small Molecule Inhibitor.Frontiers in pharmacology · 2022Article
- Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Regulation of acid-sensing ion channels by protein binding partners.Channels (Austin, Tex.) · 2021Article
Corrections and comments
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Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acid-sensing ion channels (ASICs) have emerged as important, albeit challenging therapeutic targets for pain, stroke, etc. One approach to developing therapeutic agents could involve the generation of functional antibodies against these channels. To select such antibodies, we used channels assembled in nanodiscs, such that the target ASIC1a has a configuration as close as possible to its natural state in the plasma membrane. This methodology allowed selection of functional antibodies that inhibit acid-induced opening of the channel in a dose-dependent way. In addition to regulation of pH, these antibodies block the transport of cations, including calcium, thereby preventing acid-induced cell death in vitro and in vivo. As proof of concept for the use of these antibodies to modulate ion channels in vivo, we showed that they potently protect brain cells from death after an ischemic stroke. Thus, the methodology described here should be general, thereby allowing selection of antibodies to other important ASICs, such as those involved in pain, neurodegeneration, and other conditions.
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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.