Abstract
Neurotrophic factors comprise a broad family of secreted proteins that have growth promoting, survival promoting and differentiation inducing activities. Disruption of neurotrophic factor signalling is a characteristic of many central and peripheral nervous system disorders, such as Alzheimers disease, Parkinsons disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke, and peripheral neuropathy and pain. It follows that treating patients with neurotrophic factors might be beneficial in a range of neurological diseases. However, the promising results seen in animal models of disease have not translated well into clinical trials due to the poor pharmacokinetics associated with the intact proteins, in particular, their short in vivo half-life, low blood brain barrier permeability, limited diffusion, and undesirable effects through multiple receptor interactions. This has been the main motivation for the design of small molecule modulators of the neurotrophic factor pathways. The review gives a brief survey of the various strategies to design mimetics that have been reported in the literature with special emphasis on the tandem repeat peptide agonist approach for BDNF/NT-4/5 and N-cadherin mimetics.
CNS & Neurological Disorders - Drug Targets
Title: Tandem Repeat Peptide Strategy for the Design of Neurotrophic Factor Mimetics
Volume: 7 Issue: 1
Author(s): Gareth Williams, Gareth Williams, Francisco Molina-Holgado, Francisco Molina-Holgado, Patrick Doherty and Patrick Doherty
Affiliation:
Abstract: Neurotrophic factors comprise a broad family of secreted proteins that have growth promoting, survival promoting and differentiation inducing activities. Disruption of neurotrophic factor signalling is a characteristic of many central and peripheral nervous system disorders, such as Alzheimers disease, Parkinsons disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke, and peripheral neuropathy and pain. It follows that treating patients with neurotrophic factors might be beneficial in a range of neurological diseases. However, the promising results seen in animal models of disease have not translated well into clinical trials due to the poor pharmacokinetics associated with the intact proteins, in particular, their short in vivo half-life, low blood brain barrier permeability, limited diffusion, and undesirable effects through multiple receptor interactions. This has been the main motivation for the design of small molecule modulators of the neurotrophic factor pathways. The review gives a brief survey of the various strategies to design mimetics that have been reported in the literature with special emphasis on the tandem repeat peptide agonist approach for BDNF/NT-4/5 and N-cadherin mimetics.
Export Options
About this article
Cite this article as:
Williams Gareth, Williams Gareth, Molina-Holgado Francisco, Molina-Holgado Francisco, Doherty Patrick and Doherty Patrick, Tandem Repeat Peptide Strategy for the Design of Neurotrophic Factor Mimetics, CNS & Neurological Disorders - Drug Targets 2008; 7 (1) . https://dx.doi.org/10.2174/187152708783885200
DOI https://dx.doi.org/10.2174/187152708783885200 |
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
-
5-Adenosine Monophosphate-Activated Protein Kinase and the Metabolic Syndrome
Endocrine, Metabolic & Immune Disorders - Drug Targets Molecular Chaperone ORP150 in ER Stress–related Diseases
Current Pharmaceutical Design Editorial [Hot Topic: Regulation of Glutamate Synthesis Via Inhibition of Glutamate Carboxypeptidase II (GCPII): An Effective Method to Treat Central and Peripheral Nervous System Disorders (Guest Editors: Guido Cavaletti and Barbara Slusher)]
Current Medicinal Chemistry Intracompartmental Delivery of CNTF as Therapy for Huntingtons Disease and Retinitis Pigmentosa
Current Gene Therapy Common Themes in RNA Subcellular Transport, Stress Granule Formation and Abnormal Protein Aggregation
Current Chemical Biology Motor Neuron Disease and Acquired Axonal Neuropathy Association in HIV Infection: Case Report and Update
Current HIV Research The Multiple Layers of Signaling Selectivity at Protease-Activated Receptors
Current Pharmaceutical Design Editorial [ Therapeutics for Protein Misfolding Diseases Executive Editor: Claudio Soto ]
Current Pharmaceutical Design An Update in the Management of Obesity: The Weight of CNS Targets
Recent Patents on CNS Drug Discovery (Discontinued) Management of Glia-Mediated Neuroinflammation and Related Patents
Recent Patents on Inflammation & Allergy Drug Discovery Stem Cells: An Overview of the Current Status of Therapies for Central and Peripheral Nervous System Diseases
Current Medicinal Chemistry Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options
Current Neuropharmacology Genistein: A Phytoestrogen with Multifaceted Therapeutic Properties
Mini-Reviews in Medicinal Chemistry Genetics of Alzheimer's Disease and Frontotemporal Dementia
Current Molecular Medicine CypD: The Key to the Death Door
CNS & Neurological Disorders - Drug Targets The Endocrine Regulation of Stem Cells: Physiological Importance and Pharmacological Potentials for Cell-Based Therapy
Current Stem Cell Research & Therapy Current Clinical Applications of In Vivo Magnetic Resonance Spectroscopy and Spectroscopic Imaging
Current Medical Imaging Transthyretin Deposition in Familial Amyloidotic Polyneuropathy
Current Medicinal Chemistry Thiopurine Biotransformation and Pharmacological Effects: Contribution of Oxidative Stress
Current Drug Metabolism Possible Neuroprotective Strategies in ALS
Current Neuropharmacology