Neurotrophic and metabotrophic potential of nerve growth factor and brain-derived neurotrophic factor： Linking cardiometabolic and neuropsychiatric diseases

摘要

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.