Review
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World J Pharmacol. Dec 9, 2013; 2(4): 92-99
Published online Dec 9, 2013. doi: 10.5497/wjp.v2.i4.92
Neurotrophic and metabotrophic potential of nerve growth factor and brain-derived neurotrophic factor: Linking cardiometabolic and neuropsychiatric diseases
Stanislav Yanev, Luigi Aloe, Marco Fiore, George N Chaldakov
Stanislav Yanev, Institute of Neurobiology, Department of Drug Toxicology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Luigi Aloe, Marco Fiore, Institute of Cellular Biology and Neurobiology, National Research Council, I-00168 Rome, Italy
George N Chaldakov, Laboratory of Cell Biology, Department of Anatomy and Histology, Medical University, BG-9002 Varna, Bulgaria
Author contributions: All the authors contributed to this paper equally.
Correspondence to: George N Chaldakov, MD, PhD, Laboratory of Cell Biology, Department of Anatomy and Histology, Medical University, 55 Marin Drinov Street, BG-9002 Varna, Bulgaria. chaldakov@yahoo.com
Telephone: +359-52-754394 Fax: +359-52-650019
Received: July 30, 2013
Revised: September 20, 2013
Accepted: October 16, 2013
Published online: December 9, 2013
Abstract

One of biggest recent achievements of neurobiology is the study on neurotrophic factors. The neurotrophins are exciting examples of these factors. They belong to a family of proteins consisting of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, NT-6, and NT-7. Today, NGF and BDNF are well recognized to mediate a dizzying number of trophobiological effects, ranging from neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. These are implicated in the pathogenesis of various diseases. In the same vein, recent studies in adipobiology reveal that this tissue is the body’s largest endocrine and paracrine organ producing multiple signaling proteins collectively termed adipokines, with NGF and BDNF being also produced from adipose tissue. Altogether, neurobiology and adipobiology contribute to the improvement of our knowledge on diseases beyond obesity such as cardiometabolic (atherosclerosis, type 2 diabetes, and metabolic syndrome) and neuropsychiatric (e.g., Alzheimer’s disease and depression) diseases. The present review updates evidence for (1) neurotrophic and metabotrophic potentials of NGF and BDNF linking the pathogenesis of these diseases, and (2) NGF- and BDNF-mediated effects in ampakines, NMDA receptor antagonists, antidepressants, selective deacetylase inhibitors, statins, peroxisome proliferator-activated receptor gamma agonists, and purinergic P2X3 receptor up-regulation. This may help to construct a novel paradigm in the field of translational pharmacology of neuro-metabotrophins, particularly NGF and BDNF.

Keywords: Neurotrophins, Metabotrophins, Adipose tissue, Adipokines, Disease, Therapy

Core tip: Previously we reviewed an enlarged list of metabotrophins including the adipose-produced nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), leptin and adiponectin as relevant to cardiometabolic, neurological and psychiatric diseases (Riv Psichiatr 2009; 44: 79-87). Now we update the growing body of evidence that NGF-BDNF/TrkA, B dysfunction may synergistically leads to both cardiometabolic and neuropsychiatric diseases. This may help to construct a conceptually novel therapeutic approach for future studies in the field of translational pharmacology of NGF and BDNF.