{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T20:24:21Z","timestamp":1781814261699,"version":"3.54.5"},"reference-count":92,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Many routes may lead to the transition from a healthy to a diseased phenotype. However, there are not so many routes to travel in the opposite direction; that is, therapy for different diseases. The following pressing question thus remains: what are the pathogenic routes and how can be they counteracted for therapeutic purposes? Human cells contain &gt;500 protein kinases and nearly 200 protein phosphatases, acting on thousands of proteins, including cell growth factors. We herein discuss neurotrophins with pathogenic or metabotrophic abilities, particularly brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), pro-NGF, neurotrophin-3 (NT-3), and their receptor Trk (tyrosine receptor kinase; pronounced \u201ctrack\u201d). Indeed, we introduced the word trackins, standing for Trk-targeting drugs, that play an agonistic or antagonistic role in the function of TrkBBDNF, TrkCNT\u22123, TrkANGF, and TrkApro-NGF receptors. Based on our own published results, supported by those of other authors, we aim to update and enlarge our trackins concept, focusing on (1) agonistic trackins as possible drugs for (1a) neurotrophin-deficiency cardiometabolic disorders (hypertension, atherosclerosis, type 2 diabetes mellitus, metabolic syndrome, obesity, diabetic erectile dysfunction and atrial fibrillation) and (1b) neurodegenerative diseases (Alzheimer\u2019s disease, Parkinson\u2019s disease, and multiple sclerosis), and (2) antagonistic trackins, particularly TrkANGF inhibitors for prostate and breast cancer, pain, and arrhythmogenic right-ventricular dysplasia. Altogether, the druggability of TrkANGF, TrkApro-NGF, TrkBBDNF, and TrkCNT\u22123 receptors via trackins requires a further translational pursuit. This could provide rewards for our patients.<\/jats:p>","DOI":"10.3390\/ph17070961","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T14:16:38Z","timestamp":1721398598000},"page":"961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Trackins (Trk-Targeting Drugs): A Novel Therapy for Different Diseases"],"prefix":"10.3390","volume":"17","author":[{"given":"George N.","family":"Chaldakov","sequence":"first","affiliation":[{"name":"Departments of Anatomy and Cell Biology and Translational Stem Cell Biology, Research Institute, Medical University, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Aloe","sequence":"additional","affiliation":[{"name":"Fondazione Iret, Tecnopolo R. Levi-Montalcini, Ozzano dell\u2019Emilia, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav G.","family":"Yanev","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-9715","authenticated-orcid":false,"given":"Marco","family":"Fiore","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, National Research Council, IBBC-CNR, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton B.","family":"Tonchev","sequence":"additional","affiliation":[{"name":"Departments of Anatomy and Cell Biology and Translational Stem Cell Biology, Research Institute, Medical University, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1768-3894","authenticated-orcid":false,"given":"Manlio","family":"Vinciguerra","sequence":"additional","affiliation":[{"name":"Department of Translational Stem Cell Biology, Research Institute, Medical University, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai T.","family":"Evtimov","sequence":"additional","affiliation":[{"name":"Department of Urology, University St Anna Hospital, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ghenev","sequence":"additional","affiliation":[{"name":"Department of General and Clinical Pathology, Medical University, 9002 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krikor","family":"Dikranian","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Medical School, Washington University, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1126\/science.3306916","article-title":"The nerve growth factor 35 years later","volume":"237","year":"1987","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1073\/pnas.40.10.1014","article-title":"A Nerve Growth-Stimulating Factor Isolated from Sarcomas 37 and 180","volume":"40","author":"Cohen","year":"1954","journal-title":"Proc. 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