{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T13:36:15Z","timestamp":1787405775553,"version":"build-2736575974"},"reference-count":42,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1124\/molpharm.121.000301","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T04:10:12Z","timestamp":1630469412000},"page":"491-501","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"title":["Therapeutic Neuroprotection by an Engineered Neurotrophin that Selectively Activates Tropomyosin Receptor Kinase (Trk) Family Neurotrophin Receptors but Not the p75 Neurotrophin Receptor"],"prefix":"10.1016","volume":"100","author":[{"given":"Fouad","family":"Brahimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Galan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sairey","family":"Siegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Szobota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinko V.","family":"Sarunic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan C.","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Uri","family":"Saragovi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/molpharm.121.000301_bib1","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1124\/mol.111.071332","article-title":"Ligand-dependent TrkA activity in brain differentially affects spatial learning and long-term memory","volume":"80","author":"Aboulkassim","year":"2011","journal-title":"Mol Pharmacol"},{"key":"10.1124\/molpharm.121.000301_bib2","doi-asserted-by":"crossref","first-page":"39392","DOI":"10.1074\/jbc.M110.147801","article-title":"Chronic and acute models of retinal neurodegeneration TrkA activity are neuroprotective whereas p75NTR activity is neurotoxic through a paracrine mechanism","volume":"285","author":"Bai","year":"2010","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000301_bib3","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.1167\/iovs.09-5032","article-title":"An agonistic TrkB mAb causes sustained TrkB activation, delays RGC death, and protects the retinal structure in optic nerve axotomy and in glaucoma","volume":"51","author":"Bai","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1124\/molpharm.121.000301_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0199079","article-title":"The route of administration influences the therapeutic index of an anti-proNGF neutralizing mAb for experimental treatment of diabetic retinopathy","volume":"13","author":"Barcelona","year":"2018","journal-title":"PLoS One"},{"key":"10.1124\/molpharm.121.000301_bib5","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1128\/MCB.00544-15","article-title":"A pro-nerve growth factor (proNGF) and NGF binding protein, \u03b12-macroglobulin, differentially regulates p75 and TrkA receptors and is relevant to neurodegeneration ex vivo and in vivo","volume":"35","author":"Barcelona","year":"2015","journal-title":"Mol Cell Biol"},{"key":"10.1124\/molpharm.121.000301_bib6","doi-asserted-by":"crossref","first-page":"8826","DOI":"10.1523\/JNEUROSCI.4278-15.2016","article-title":"p75NTR and its ligand ProNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy","volume":"36","author":"Barcelona","year":"2016","journal-title":"J Neurosci"},{"key":"10.1124\/molpharm.121.000301_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2020.101447","article-title":"Alternative splicing of a receptor intracellular domain yields different ectodomain conformations, enabling isoform-selective functional ligands","volume":"23","author":"Brahimi","year":"2020","journal-title":"iScience"},{"key":"10.1124\/molpharm.121.000301_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0089617","article-title":"Combinatorial assembly of small molecules into bivalent antagonists of TrkC or TrkA receptors","volume":"9","author":"Brahimi","year":"2014","journal-title":"PLoS One"},{"key":"10.1124\/molpharm.121.000301_bib9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0162307","article-title":"The paradoxical signals of two TrkC receptor isoforms supports a rationale for novel therapeutic strategies in ALS","volume":"11","author":"Brahimi","year":"2016","journal-title":"PLoS One"},{"key":"10.1124\/molpharm.121.000301_bib10","doi-asserted-by":"crossref","first-page":"8009","DOI":"10.1523\/JNEUROSCI.1508-04.2004","article-title":"Long-lasting rescue of age-associated deficits in cognition and the CNS cholinergic phenotype by a partial agonist peptidomimetic ligand of TrkA","volume":"24","author":"Bruno","year":"2004","journal-title":"J Neurosci"},{"key":"10.1124\/molpharm.121.000301_bib11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1042\/CS20050163","article-title":"Neurotrophin signalling in health and disease","volume":"110","author":"Chao","year":"2006","journal-title":"Clin Sci (Lond)"},{"key":"10.1124\/molpharm.121.000301_bib12","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.expneurol.2013.06.013","article-title":"A multifunctional neurotrophin with reduced affinity to p75NTR enhances transplanted Schwann cell survival and axon growth after spinal cord injury","volume":"248","author":"Enomoto","year":"2013","journal-title":"Exp Neurol"},{"key":"10.1124\/molpharm.121.000301_bib13","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1167\/iovs.16-20988","article-title":"Subconjunctival delivery of p75NTR antagonists reduces the inflammatory, vascular, and neurodegenerative pathologies of diabetic retinopathy","volume":"58","author":"Galan","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1124\/molpharm.121.000301_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0101349","article-title":"Neuronal injury external to the retina rapidly activates retinal glia, followed by elevation of markers for cell cycle re-entry and death in retinal ganglion cells","volume":"9","author":"Galan","year":"2014","journal-title":"PLoS One"},{"key":"10.1124\/molpharm.121.000301_bib15","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1038\/s41419-017-0074-8","article-title":"In retinitis pigmentosa TrkC.T1-dependent vectorial Erk activity upregulates glial TNF-\u03b1, causing selective neuronal death","volume":"8","author":"Gal\u00e1n","year":"2017","journal-title":"Cell Death Dis"},{"key":"10.1124\/molpharm.121.000301_bib16","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/dneu.20776","article-title":"An agonistic mAb directed to the TrkC receptor juxtamembrane region defines a trophic hot spot and interactions with p75 coreceptors","volume":"70","author":"Guillemard","year":"2010","journal-title":"Dev Neurobiol"},{"key":"10.1124\/molpharm.121.000301_bib17","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/pro.5560050306","article-title":"Mutational studies of conserved residues in the dimer interface of nerve growth factor","volume":"5","author":"Guo","year":"1996","journal-title":"Protein Sci"},{"key":"10.1124\/molpharm.121.000301_bib18","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0959-4388(02)00321-5","article-title":"The many faces of p75NTR","volume":"12","author":"Hempstead","year":"2002","journal-title":"Curr Opin Neurobiol"},{"key":"10.1124\/molpharm.121.000301_bib19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2174\/156720506775697061","article-title":"Dissecting the diverse actions of pro- and mature neurotrophins","volume":"3","author":"Hempstead","year":"2006","journal-title":"Curr Alzheimer Res"},{"key":"10.1124\/molpharm.121.000301_bib20","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.tins.2012.03.007","article-title":"p75 neurotrophin receptor signaling in nervous system injury and degeneration: paradox and opportunity","volume":"35","author":"Ib\u00e1\u00f1ez","year":"2012","journal-title":"Trends Neurosci"},{"key":"10.1124\/molpharm.121.000301_bib21","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1038\/sj.onc.1206864","article-title":"Differential cross-regulation of TrkA and TrkC tyrosine kinase receptors with p75","volume":"22","author":"Ivanisevic","year":"2003","journal-title":"Oncogene"},{"key":"10.1124\/molpharm.121.000301_bib22","doi-asserted-by":"crossref","first-page":"16754","DOI":"10.1074\/jbc.M701996200","article-title":"TrkA receptor \u201chot spots\u201d for binding of NT-3 as a heterologous ligand","volume":"282","author":"Ivanisevic","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000301_bib23","doi-asserted-by":"crossref","first-page":"56007","DOI":"10.1117\/1.JBO.18.5.056007","article-title":"Adaptive optics optical coherence tomography for in vivo mouse retinal imaging","volume":"18","author":"Jian","year":"2013","journal-title":"J Biomed Opt"},{"key":"10.1124\/molpharm.121.000301_bib24","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.nbd.2016.08.004","article-title":"Neurotrophin receptor agonists and antagonists as therapeutic agents: an evolving paradigm","volume":"97","author":"Josephy-Hernandez","year":"2017","journal-title":"Neurobiol Dis"},{"key":"10.1124\/molpharm.121.000301_bib25","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1073\/pnas.0909276107","article-title":"ProNGF induces TNFalpha-dependent death of retinal ganglion cells through a p75NTR non-cell-autonomous signaling pathway","volume":"107","author":"Lebrun-Julien","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/molpharm.121.000301_bib26","doi-asserted-by":"crossref","first-page":"5536","DOI":"10.1523\/JNEUROSCI.0831-09.2009","article-title":"Excitotoxic death of retinal neurons in vivo occurs via a non-cell-autonomous mechanism","volume":"29","author":"Lebrun-Julien","year":"2009","journal-title":"J Neurosci"},{"key":"10.1124\/molpharm.121.000301_bib27","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.mcn.2008.12.005","article-title":"Inhibition of p75(NTR) in glia potentiates TrkA-mediated survival of injured retinal ganglion cells","volume":"40","author":"Lebrun-Julien","year":"2009","journal-title":"Mol Cell Neurosci"},{"key":"10.1124\/molpharm.121.000301_bib28","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrd4024","article-title":"Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease","volume":"12","author":"Longo","year":"2013","journal-title":"Nat Rev Drug Discov"},{"key":"10.1124\/molpharm.121.000301_bib29","doi-asserted-by":"crossref","first-page":"33600","DOI":"10.1074\/jbc.M109.058420","article-title":"Identification of critical residues within the conserved and specificity patches of nerve growth factor leading to survival or differentiation","volume":"284","author":"Mahapatra","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000301_bib30","doi-asserted-by":"crossref","first-page":"6031","DOI":"10.1523\/JNEUROSCI.17-16-06031.1997","article-title":"Optimal nerve growth factor trophic signals mediated by synergy of TrkA and p75 receptor-specific ligands","volume":"17","author":"Maliartchouk","year":"1997","journal-title":"J Neurosci"},{"key":"10.1124\/molpharm.121.000301_bib31","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1007\/s00125-020-05222-4","article-title":"Antagonism of proNGF or its receptor p75NTR reverses remodelling and improves bladder function in a mouse model of diabetic voiding dysfunction","volume":"63","author":"Mossa","year":"2020","journal-title":"Diabetologia"},{"key":"10.1124\/molpharm.121.000301_bib32","doi-asserted-by":"crossref","first-page":"e2922","DOI":"10.1038\/cddis.2017.306","article-title":"p75NTR antagonists attenuate photoreceptor cell loss in murine models of retinitis pigmentosa","volume":"8","author":"Plat\u00f3n-Corchado","year":"2017","journal-title":"Cell Death Dis"},{"key":"10.1124\/molpharm.121.000301_bib33","doi-asserted-by":"crossref","first-page":"33085","DOI":"10.1074\/jbc.272.52.33085","article-title":"A second determinant of binding to the p75 neurotrophin receptor revealed by alanine-scanning mutagenesis of a conserved loop in nerve growth factor","volume":"272","author":"Ryd\u00e9n","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000301_bib34","doi-asserted-by":"crossref","first-page":"5623","DOI":"10.1074\/jbc.271.10.5623","article-title":"Binding of neurotrophin-3 to p75LNGFR, TrkA, and TrkB mediated by a single functional epitope distinct from that recognized by trkC","volume":"271","author":"Ryd\u00e9n","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000301_bib35","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3389\/fncel.2019.00231","article-title":"Neuroprotection: pro-survival and anti-neurotoxic mechanisms as therapeutic strategies in neurodegeneration","volume":"13","author":"Saragovi","year":"2019","journal-title":"Front Cell Neurosci"},{"key":"10.1124\/molpharm.121.000301_bib36","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2174\/156720509789207912","article-title":"A neurotrophic rationale for the therapy of neurodegenerative disorders","volume":"6","author":"Saragovi","year":"2009","journal-title":"Curr Alzheimer Res"},{"key":"10.1124\/molpharm.121.000301_bib37","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/dneu.20360","article-title":"Neurotrophic rationale in glaucoma: a TrkA agonist, but not NGF or a p75 antagonist, protects retinal ganglion cells in vivo","volume":"67","author":"Shi","year":"2007","journal-title":"Dev Neurobiol"},{"key":"10.1124\/molpharm.121.000301_bib38","doi-asserted-by":"crossref","first-page":"18712","DOI":"10.1523\/JNEUROSCI.1310-13.2013","article-title":"A small molecule TrkB ligand reduces motor impairment and neuropathology in R6\/2 and BACHD mouse models of Huntington\u2019s disease","volume":"33","author":"Simmons","year":"2013","journal-title":"J Neurosci"},{"key":"10.1124\/molpharm.121.000301_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0224022","article-title":"BDNF, NT-3 and Trk receptor agonist monoclonal antibodies promote neuron survival, neurite extension, and synapse restoration in rat cochlea ex vivo models relevant for hidden hearing loss","volume":"14","author":"Szobota","year":"2019","journal-title":"PLoS One"},{"key":"10.1124\/molpharm.121.000301_bib40","doi-asserted-by":"crossref","first-page":"4775","DOI":"10.1021\/bi962877+","article-title":"Specificity determinants in neurotrophin-3 and design of nerve growth factor-based trkC agonists by changing central beta-strand bundle residues to their neurotrophin-3 analogs","volume":"36","author":"Urfer","year":"1997","journal-title":"Biochemistry"},{"key":"10.1124\/molpharm.121.000301_bib41","doi-asserted-by":"crossref","first-page":"5896","DOI":"10.1002\/j.1460-2075.1994.tb06935.x","article-title":"The binding epitopes of neurotrophin-3 to its receptors trkC and gp75 and the design of a multifunctional human neurotrophin","volume":"13","author":"Urfer","year":"1994","journal-title":"EMBO J"},{"key":"10.1124\/molpharm.121.000301_bib42","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.chembiol.2005.06.015","article-title":"Selective small molecule peptidomimetic ligands of TrkC and TrkA receptors afford discrete or complete neurotrophic activities","volume":"12","author":"Zaccaro","year":"2005","journal-title":"Chem Biol"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24011751?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24011751?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/molpharm.121.000301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T08:47:31Z","timestamp":1739954851000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24011751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["S0026895X24011751"],"URL":"https:\/\/doi.org\/10.1124\/molpharm.121.000301","relation":{},"ISSN":["0026-895X"],"issn-type":[{"value":"0026-895X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Therapeutic Neuroprotection by an Engineered Neurotrophin that Selectively Activates Tropomyosin Receptor Kinase (Trk) Family Neurotrophin Receptors but Not the p75 Neurotrophin Receptor","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/molpharm.121.000301","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}