Abstract
Ligand-independent and/or proNGF-induced p75NTR signaling has emerged as a potential major contributor to a number of pathological states, including axotomy-induced death, motor neuron degeneration, neuronal degeneration in Alzheimers disease and oligodendrocyte death following spinal cord injury. A long standing goal in the neurotrophin field has been the development of non-peptide, small molecules capable of functioning as specific ligands at neurotrophin receptors such as p75NTR to promote desired biological outcomes. Synthetic peptides modeled on neurotrophin protein domains have been found to bind to and activate various neurotrophin receptors, raising the possibility that active, nonpeptide, small molecule ligands might also be identified; however, traditional high-throughput screening approaches have been largely ineffective in identifying such compounds. Using pharmacophores derived from the structure of loop 1 of nerve growth factor, non-peptide, small molecules that function as p75NTR ligands to promote survival and block proNGFinduced death have recently been identified. Small molecule p75NTR ligands, with high potency and specificity, may provide novel therapeutic approaches for neurodegenerative diseases, neurotrauma and other pathologic states.
CNS & Neurological Disorders - Drug Targets
Title: Small Molecule Modulation of p75 Neurotrophin Receptor Functions
Volume: 7 Issue: 1
Author(s): Frank M. Longo, Frank M. Longo, Stephen M. Massa and Stephen M. Massa
Affiliation:
Abstract: Ligand-independent and/or proNGF-induced p75NTR signaling has emerged as a potential major contributor to a number of pathological states, including axotomy-induced death, motor neuron degeneration, neuronal degeneration in Alzheimers disease and oligodendrocyte death following spinal cord injury. A long standing goal in the neurotrophin field has been the development of non-peptide, small molecules capable of functioning as specific ligands at neurotrophin receptors such as p75NTR to promote desired biological outcomes. Synthetic peptides modeled on neurotrophin protein domains have been found to bind to and activate various neurotrophin receptors, raising the possibility that active, nonpeptide, small molecule ligands might also be identified; however, traditional high-throughput screening approaches have been largely ineffective in identifying such compounds. Using pharmacophores derived from the structure of loop 1 of nerve growth factor, non-peptide, small molecules that function as p75NTR ligands to promote survival and block proNGFinduced death have recently been identified. Small molecule p75NTR ligands, with high potency and specificity, may provide novel therapeutic approaches for neurodegenerative diseases, neurotrauma and other pathologic states.
Export Options
About this article
Cite this article as:
Longo M. Frank, Longo M. Frank, Massa M. Stephen and Massa M. Stephen, Small Molecule Modulation of p75 Neurotrophin Receptor Functions, CNS & Neurological Disorders - Drug Targets 2008; 7 (1) . https://dx.doi.org/10.2174/187152708783885093
DOI https://dx.doi.org/10.2174/187152708783885093 |
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
-
Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) TRPV1 and Synaptic Transmission
Current Pharmaceutical Biotechnology The Emerging Role of TRP Channels in Mechanisms of Temperature and Pain Sensation
Current Neuropharmacology Ginger and Heart Health: From Mechanisms to Therapeutics
Current Molecular Pharmacology Pituitary Stem Cells Drop Their Mask
Current Stem Cell Research & Therapy Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment
CNS & Neurological Disorders - Drug Targets TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids and Nociceptive Signalling
Current Neuropharmacology Chemistry, Biological Properties and SAR Analysis of Quinoxalinones
Mini-Reviews in Medicinal Chemistry Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair
CNS & Neurological Disorders - Drug Targets Biochemistry and Neurobiology of Prosaposin: A Potential Therapeutic Neuro-Effector
Central Nervous System Agents in Medicinal Chemistry Concept of Comprehensive Treatment for Osteoarthritis (OA)
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Advancing Drug Therapy for Brain Tumours: A Current Review of the Pro-inflammatory Peptide Substance P and its Antagonists as Anti-cancer Agents
Recent Patents on CNS Drug Discovery (Discontinued) Application of Decoy Oligonucleotides as Novel Therapeutic Strategy: A Contemporary Overview
Current Drug Discovery Technologies Therapeutic Gene Products Delivery by Neuron Stem Cells
Current Pharmaceutical Biotechnology NK-1 Receptor Antagonists: A New Generation of Anticancer Drugs
Mini-Reviews in Medicinal Chemistry Targeting the Toll of Drug Abuse: The Translational Potential of Toll-Like Receptor 4
CNS & Neurological Disorders - Drug Targets AMPK Function in Aging Process
Current Drug Targets Voltage-Gated Sodium Channels and Pain
Current Drug Targets - CNS & Neurological Disorders Therapeutic Option of Plasmid-DNA Based Gene Transfer
Current Topics in Medicinal Chemistry Neutralizing Endogenous VEGF Following Traumatic Spinal Cord Injury Modulates Microvascular Plasticity but not Tissue Sparing or Functional Recovery
Current Neurovascular Research