ArticleCell death & disease2012
Low molecular weight, non-peptidic agonists of TrkA receptor with NGF-mimetic activity.
Article in Cell death & disease, 2012. 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 23 papers.
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Who cites it
23 citing papers in PubMed, 70 citations in OpenAlex.
- Small-Molecule Trk Agonists: Where Do We Go from Here?Journal of medicinal chemistry · 2025Review
- Multimodal beneficial effects of BNN27, a nerve growth factor synthetic mimetic, in the 5xFAD mouse model of Alzheimer's disease.Molecular psychiatry · 2025Article
- Neurotrophin mimetics and tropomyosin kinase receptors: a futuristic pharmacological tool for Parkinson's.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- A bone to pick-cellular and molecular mechanisms of bone pain in sickle cell disease.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Development and Biological Characterization of a Novel Selective TrkA Agonist with Neuroprotective Properties against Amyloid Toxicity.Biomedicines · 2022Article
- Article
- The Neurotrophic-Like Effect of Carvacrol: Perspective for Axonal and Synaptic Regeneration.Neurotoxicity research · 2021Article
- Ligand bias in receptor tyrosine kinase signaling.The Journal of biological chemistry · 2020Review
- hNGF Peptides Elicit the NGF-TrkA Signalling Pathway in Cholinergic Neurons and Retain Full Neurotrophic Activity in the DRG Assay.Biomolecules · 2020Article
- Article
- Current Status of Drug Targets and Emerging Therapeutic Strategies in the Management of Alzheimer's Disease.Current neuropharmacology · 2020Review
- Article
- Innovative Therapy for Alzheimer's Disease-With Focus on Biodelivery of NGF.Frontiers in neuroscience · 2019Review
- Modulation of ERK1/2 and Akt Pathways Involved in the Neurotrophic Action of Caffeic Acid Alkyl Esters.Molecules (Basel, Switzerland) · 2018Article
- Bridging pro-inflammatory signals, synaptic transmission and protection in spinal explants in vitro.Molecular brain · 2018Article
- The Emerging Therapeutic Role of NGF in Alzheimer's Disease.Neurochemical research · 2016Review
- The p75 neurotrophin receptor: at the crossroad of neural repair and death.Neural regeneration research · 2015Review
- Dynamic nature of the p75 neurotrophin receptor in response to injury and disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Review
- Diversity-oriented synthesis as a tool for chemical genetics.Molecules (Basel, Switzerland) · 2014Review
- A new molecular explanation for age-related neurodegeneration: the Tyr682 residue of amyloid precursor protein.BioEssays : news and reviews in molecular, cellular and developmental biology · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exploitation of the biologic activity of neurotrophins is desirable for medical purposes, but their protein nature intrinsically bears adverse pharmacokinetic properties. Here, we report synthesis and biologic characterization of a novel class of low molecular weight, non-peptidic compounds with NGF (nerve growth factor)-mimetic properties. MT2, a representative compound, bound to Trk (tropomyosin kinase receptor)A chain on NGF-sensitive cells, as well as in cell-free assays, at nanomolar concentrations and induced TrkA autophosphorylation and receptor-mediated internalization. MT2 binding involved at least two amino-acid residues within TrkA molecule. Like NGF, MT2 increased phosphorylation of extracellular signal-regulated kinase1/2 and Akt proteins and production of MKP-1 phosphatase (dual specificity phosphatase 1), modulated p38 mitogen-activated protein kinase activation, sustained survival of serum-starved PC12 or RDG cells, and promoted their differentiation. However, the intensity of such responses was heterogenous, as the ability of maintaining survival was equally possessed by NGF and MT2, whereas the induction of differentiation was expressed at definitely lower levels by the mimetic. Analysis of TrkA autophosphorylation patterns induced by MT2 revealed a strong tyrosine (Tyr)490 and a limited Tyr785 and Tyr674/675 activation, findings coherent with the observed functional divarication. Consistently, in an NGF-deprived rat hippocampal neuronal model of Alzheimer Disease, MT2 could correct the biochemical abnormalities and sustain cell survival. Thus, NGF mimetics may reveal interesting investigational tools in neurobiology, as well as promising drug candidates.
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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.