ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. 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 67 papers, 1 of them a synthesis that pooled it.
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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
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Transactivation of receptor tyrosine kinases by purinergic P2Y and adenosine receptors.Purinergic signalling · 2023Pooled it
- Ubiquitin Proteasome System Components, RAD23A and USP13, Modulate TDP-43 Solubility and Neuronal Toxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins.bioRxiv : the preprint server for biology · 2025Article
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- Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry.Communications biology · 2023Article
- Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?Molecules (Basel, Switzerland) · 2023Review
- Neurotrophic factors in the physiology of motor neurons and their role in the pathobiology and therapeutic approach to amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2023Review
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- The Multifaceted Role of GPCRs in Amyotrophic Lateral Sclerosis: A New Therapeutic Perspective?International journal of molecular sciences · 2022Review
- Allosteric modulation of the adenosine AeLife · 2022Article
- Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- The nuclear ubiquitin ligase adaptor SPOP is a conserved regulator of C9orf72 dipeptide toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- How Are Adenosine and Adenosine ABiomedicines · 2021Review
- Exosome microRNAs in Amyotrophic Lateral Sclerosis: A Pilot Study.Biomolecules · 2021Article
- Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
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- GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration.International journal of molecular sciences · 2020Review
- Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition.Experimental neurology · 2020Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedRussell, David [corrected to Russell, David S]
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The death of motor neurons in amyotrophic lateral sclerosis (ALS) is thought to result from the interaction of a variety of factors including excitotoxicity, accumulation of toxic proteins, and abnormal axonal transport. Previously, we found that the susceptibility of motor neurons to excitotoxic insults can be limited by inhibiting signals evoked by brain-derived neurotrophic factor (BDNF) activation of the receptor tyrosine kinase B (TrkB). Here we show that this can be achieved by direct kinase inhibition or by blockade of a transactivation pathway that uses adenosine A2a receptors and src-family kinases (SFKs). Downstream signaling cascades (such as mitogen-activated protein kinase and phosphatidylinositol-3 kinase) are inhibited by these blockers. In addition to protecting motor neurons from excitotoxic insult, these agents also prevent toxicity that follows from the expression of mutant proteins (G85R superoxide dismutase 1; G59S p150(glued)) that cause familial motor neuron disease. TrkB, adenosine A2a receptors, and SFKs associate into complexes in lipid raft and nonlipid raft membranes and the signaling from lipids rafts may be particularly important because their disruption by cholesterol depletion blocks the ability of BDNF to render motor neurons vulnerable to insult. The neuroprotective versatility of Trk antagonism suggests that it may have broad utility in the treatment of ALS patients.
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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 OpenQuestion graph.