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Theragnostics of TRK-targeting agents (trackins): a challenge that promises reward

Stanislav Yanev, Luigi Aloe, Daniela Panayotova, Manlio Vinciguerra, Nikolai T. Evtimov, Anton B. Tonchev, Marco Fiore, Peter I. Ghenev, George N. Chaldakov

Abstract

Therminologically, theragnostics combines therapeutics and diagnostics. Life at cellular and molecular level is a binary event (e.g., phosphorylation-dephosphorylation of proteins, methylation-demethylations of DNA and acetylation-deacetylation of histones) aimed at the maintenance of a sanogenic phenotype of the homeostasis. Herein, we focus on the neurotrophins with metabotrophic or pathogenic potentials, particularly nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and their receptors Trk (tyrosine/tropomyosin receptor kinase; pronounced “track”). Accordingly, the term trackins was introduced which stands for Trk-targeting agents influencing agonistically or antagonistically the activity of TrkANGF, TrkBBDNF, and TrkCNT-3 receptor. We argue that multiple diseases may be trackins curable, for instance: (i) agonistic trackins may have therapeutic potentials for cardiometabolic diseases (e.g., atherosclerosis, obesity, T2DM, and metabolic syndrome) and for neurometabolic diseases (e.g., Alzheimer’s disease/T3DM), whereas (ii) antagonistic trackins may be drugs for prostate, breast, gastric, pancreatic and colon cancers, also for pain, and eye, skin and male genitourinary track diseases. Moreover, TrkANGF, TrkBBDNF and TrkCNT-3 receptor may be promising biomarkers for diagnosis and prognosis of these diseases. Altogether, the presented data may be a challenge that promises reward requiring a further pursuit.

Keywords

theragnostics,Trk-targeting agents (trackins), NGF, BDNF, NT-3, cardiometabolic diseases, cancer, Alzheimer’s disease

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DOI: http://dx.doi.org/10.14748/bmr.v33.9120

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About The Authors

Stanislav Yanev
Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia
Bulgaria

Luigi Aloe
Fondazione Iret, Tecnopolo R. Levi-Montalcini, Rome
Italy

Daniela Panayotova
Division of Cardiology, Department of Cardiac Surgery, Saint Marina University Hospital
Bulgaria

Manlio Vinciguerra
Medical University of Varna
Bulgaria

Department Translational Stem Cell Biology, Research Institute

Nikolai T. Evtimov
Department of Urology, Saint Anna Hospital, Varna
Bulgaria

Anton B. Tonchev
Medical University of Varna
Bulgaria

Departments of Anatomy and Cell Biology and Translational Stem Cell Biology, Research Institute

Marco Fiore
Institute of Biochemistry and Cell Biology, Section of Neurobiology Rita Levi-Montalcini, National Research Council (CNR), Rome
Italy

Peter I. Ghenev
Medical University of Varna
Bulgaria

Department of General and Clinical Pathology

George N. Chaldakov
Medical University of Varna
Bulgaria

Departments of Anatomy and Cell Biology and Translational Stem Cell Biology, Research Institute

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