Trackins (Trk-Targeting Drugs): A Novel Therapy for Different Diseases

• Published in: Pharmaceuticals
• Main Authors: George N. Chaldakov, Luigi Aloe, Stanislav G. Yanev, Marco Fiore, Anton B. Tonchev, Manlio Vinciguerra, Nikolai T. Evtimov, Peter Ghenev, Krikor Dikranian
• Format: Article
• Language: English
• Published: MDPI AG 2024-07-01
• Subjects: Trk-targeting drugs (trackins); Trk receptors; NGF; proNGF; BDNF; NT-3
• Online Access: https://www.mdpi.com/1424-8247/17/7/961

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 >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 “track”). Indeed, we introduced the word <i>trackins</i>, standing for Trk-targeting drugs, that play an agonistic or antagonistic role in the function of TrkB^BDNF, TrkC^NT−3, TrkA^NGF, and TrkA^pro-NGF receptors. Based on our own published results, supported by those of other authors, we aim to update and enlarge our <i>trackins concept</i>, 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’s disease, Parkinson’s disease, and multiple sclerosis), and (2) antagonistic trackins, particularly TrkA^NGF inhibitors for prostate and breast cancer, pain, and arrhythmogenic right-ventricular dysplasia. Altogether, the druggability of TrkA^NGF, TrkA^pro-NGF, TrkB^BDNF, and TrkC^NT−3 receptors via trackins requires a further translational pursuit. This could provide rewards for our patients.