ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Long-lasting rescue of age-associated deficits in cognition and the CNS cholinergic phenotype by a partial agonist peptidomimetic ligand of TrkA.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
32 citing papers in PubMed, 87 citations in OpenAlex.
- Selective Modulation of Trk Receptors byACS chemical neuroscience · 2025Article
- Selective inhibitors of the TrkC.T1 receptor reduce retinal inflammation and delay neuronal death in a model of retinitis pigmentosa.PNAS nexus · 2025Article
- Clinical and genetic characteristics of three patients with congenital insensitivity to pain with anhidrosis: Case reports and a review of the literature.Molecular genetics & genomic medicine · 2024Review
- Ultrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies.Brain : a journal of neurology · 2022Article
- Focused ultrasound delivery of a selective TrkA agonist rescues cholinergic function in a mouse model of Alzheimer's disease.Science advances · 2020Article
- Surgery, Anesthesia and Intensive Care Environment Induce Delirium-Like Behaviors and Impairment of Synaptic Function-Related Gene Expression in Aged Mice.Frontiers in aging neuroscience · 2020Article
- Exploring the Pathogenesis of Alzheimer Disease in Basal Forebrain Cholinergic Neurons: Converging Insights From Alternative Hypotheses.Frontiers in neuroscience · 2019Review
- Nerve Growth Factor Pathobiology During the Progression of Alzheimer's Disease.Frontiers in neuroscience · 2019Review
- Neuroprotection: Pro-survival and Anti-neurotoxic Mechanisms as Therapeutic Strategies in Neurodegeneration.Frontiers in cellular neuroscience · 2019Review
- Pharmacological interrogation of TrkA-mediated mechanisms in hippocampal-dependent memory consolidation.PloS one · 2019Article
- Innovative Therapy for Alzheimer's Disease-With Focus on Biodelivery of NGF.Frontiers in neuroscience · 2019Review
- Novel Technologies for Dipeptide Drugs Design and their Implantation.Current pharmaceutical design · 2018Review
- Impaired NGF/TrkA Signaling Causes Early AD-Linked Presynaptic Dysfunction in Cholinergic Primary Neurons.Frontiers in cellular neuroscience · 2017Article
- Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease.Molecular neurodegeneration · 2016Review
- The Inorganic Side of NGF: Copper(II) and Zinc(II) Affect the NGF Mimicking Signaling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor.Frontiers in neuroscience · 2016Article
- Nerve growth factor novel dipeptide mimetic GK-2 selectively activates TrkA postreceptor signaling pathways and does not cause adverse effects of native neurotrophin.Doklady. Biochemistry and biophysics · 2014Article
- Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer's Disease.Acta naturae · 2013Article
- Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease.Nature reviews. Drug discovery · 2013Review
- Correlation of cognitive performance and morphological changes in neocortical pyramidal neurons in aging.Neurobiology of aging · 2012Article
- TrkA gene ablation in basal forebrain results in dysfunction of the cholinergic circuitry.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
Previously, we developed a proteolytically stable small molecule peptidomimetic termed D3 as a selective ligand of the extracellular domain of the TrkA receptor for the NGF. Ex vivo D3 was defined as a selective, partial TrkA agonist. Here, the in vivo efficacy of D3 as a potential therapeutic for cholinergic neurons was tested in cognitively impaired aged rats, and we compared the consequence of partial TrkA activation (D3) versus full TrkA/p75 activation (NGF). We show that in vivo D3 binds to TrkA receptors and affords a significant and long-lived phenotypic rescue of the cholinergic phenotype both in the cortex and in the nucleus basalis. The cholinergic rescue was selective and correlates with a significant improvement of memory/learning in cognitively impaired aged rats. The effects of the synthetic ligand D3 and the natural ligand NGF were comparable. Small, proteolytically stable ligands with selective agonistic activity at a growth factor receptor may have therapeutic potential for neurodegenerative disorders.
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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.