Abstract
The brain-derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin-receptor-kinase B (TrkB) play a critical role in neuronal differentiation and survival, synapse plasticity, and memory. Indeed, both have been implicated in the pathophysiology of numerous diseases. Although the remarkable therapeutic potential of BDNF has generated much research over the past decade, the poor pharmacokinetics and adverse side effect profile have limited its clinical usefulness of BDNF. Small compounds that mimic BDNF’s neurotrophic signaling and overcome the pharmacokinetic and side effect barriers may have greater therapeutic potential. The purpose of this review is to provide a survey of the various strategies taken towards the development of small molecule mimetics for BDNF and the selective TrkB agonist. A particular focus was placed on TrkB agonist 7, 8-dihydroxyflavone, which modulates multiple functions and has demonstrated remarkable therapeutic efficacy in a variety of central nervous system disease models. Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB binding domains of BDNF, loop II-LM22A compounds that directly activate TrkB. These alternative molecules have shown promise in preclinical studies and may be included in prospective clinical investigations.
Keywords: Brain-derived neurotrophic factor, small molecule, Alzheimer’s disease, tropomyosin-receptor-kinase B, mimetics, CNS disorders, synaptic plasticity, learning and memory, depression.
CNS & Neurological Disorders - Drug Targets
Title:Small Molecules Activating TrkB Receptor for Treating a Variety of CNS Disorders
Volume: 12 Issue: 7
Author(s): Yan Zeng, Xiaonan Wang, Qiang Wang, Shumin Liu, Xiamin Hu and Shawn M. McClintock
Affiliation:
Keywords: Brain-derived neurotrophic factor, small molecule, Alzheimer’s disease, tropomyosin-receptor-kinase B, mimetics, CNS disorders, synaptic plasticity, learning and memory, depression.
Abstract: The brain-derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin-receptor-kinase B (TrkB) play a critical role in neuronal differentiation and survival, synapse plasticity, and memory. Indeed, both have been implicated in the pathophysiology of numerous diseases. Although the remarkable therapeutic potential of BDNF has generated much research over the past decade, the poor pharmacokinetics and adverse side effect profile have limited its clinical usefulness of BDNF. Small compounds that mimic BDNF’s neurotrophic signaling and overcome the pharmacokinetic and side effect barriers may have greater therapeutic potential. The purpose of this review is to provide a survey of the various strategies taken towards the development of small molecule mimetics for BDNF and the selective TrkB agonist. A particular focus was placed on TrkB agonist 7, 8-dihydroxyflavone, which modulates multiple functions and has demonstrated remarkable therapeutic efficacy in a variety of central nervous system disease models. Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB binding domains of BDNF, loop II-LM22A compounds that directly activate TrkB. These alternative molecules have shown promise in preclinical studies and may be included in prospective clinical investigations.
Export Options
About this article
Cite this article as:
Zeng Yan, Wang Xiaonan, Wang Qiang, Liu Shumin, Hu Xiamin and McClintock M. Shawn, Small Molecules Activating TrkB Receptor for Treating a Variety of CNS Disorders, CNS & Neurological Disorders - Drug Targets 2013; 12 (7) . https://dx.doi.org/10.2174/18715273113129990089
DOI https://dx.doi.org/10.2174/18715273113129990089 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Anti-cancer Potential of Phyto-alkaloids: A Prospective Review
Current Cancer Therapy Reviews Nongenomic Actions of Retinoids: Role of Nur77 and RXR in the Regulation of Apoptosis and Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Molecular Targeting of Cell Death Signal Transduction Pathways in Cancer
Current Signal Transduction Therapy Potential Medications or Compounds Acting on Toll-like Receptors in Cerebral Ischemia
Current Neuropharmacology New Insights about the Potential Application of the Association of Vitamins C (Sodium Ascorbate) and K3 (Menadione) as Auxiliary Therapy in Cancer Treatment
Medicinal Chemistry Reviews - Online (Discontinued) Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer
Current Vascular Pharmacology New, Substituted Derivatives of Dicarboximides and their Cytotoxic Properties
Anti-Cancer Agents in Medicinal Chemistry Immune System Modulates the Function of Adult Neural Stem Cells
Current Immunology Reviews (Discontinued) Hypoglycemia Induces Tau Hyperphosphorylation
Current Alzheimer Research Recent Developments in the Understanding and Treatment of Neurodegenerative Disorders Involving Protein Conformational Misfolding and Amyloid Formation
Medicinal Chemistry Reviews - Online (Discontinued) Non-Analgesic Effects of Opioids: Neuroprotection in the Retina
Current Pharmaceutical Design Neuronal Acetylcholine Nicotinic Receptors as New Targets for Lung Cancer Treatment
Current Pharmaceutical Design Principles and Therapeutic Relevance for Targeting Mitochondria in Aging and Neurodegenerative Diseases
Current Pharmaceutical Design The Small Heat Shock Protein HspB8: Role in Nervous System Physiology and Pathology
CNS & Neurological Disorders - Drug Targets Protein Amyloidogenesis Investigated by Small Angle Scattering
Current Pharmaceutical Design STAT Inhibition in the Treatment of Cancer: Transcription Factors as Targets for Molecular Therapy
Current Cancer Therapy Reviews From Peptides to Small Molecules: An Intriguing but Intricated Way to New Drugs
Current Medicinal Chemistry Regulators of the G1 Phase of the Cell Cycle and Neurogenesis
Central Nervous System Agents in Medicinal Chemistry Gut Emotions - Mechanisms of Action of Probiotics as Novel Therapeutic Targets for Depression and Anxiety Disorders
CNS & Neurological Disorders - Drug Targets Neurological Disorders of Purine and Pyrimidine Metabolism
Current Topics in Medicinal Chemistry