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
-
Biochemical, Biomedical and Metabolic Aspects of Imidazole-Containing Dipeptides with the Inherent Complexity to Neurodegenerative Diseases and Various States of Mental Well-Being: A Challenging Correction and Neurotherapeutic Pharmaceutical Biotechnology for Treating Cognitive Deficits, Depression and Intellectual Disabilities
Current Pharmaceutical Biotechnology Snake Venom: From Deadly Toxins to Life-saving Therapeutics
Current Medicinal Chemistry Editorial [ Neurodegenerative Disorders: From Molecules to Man (Part 2) Guest Editors: Giuseppe Di Giovanni, Vincenzo Di Matteo and Ennio Esposito ]
CNS & Neurological Disorders - Drug Targets Protein Misfolding in Disease and Small Molecule Therapies
Current Topics in Medicinal Chemistry Age-Related Changes in Motor Cortical Properties and Voluntary Activation of Skeletal Muscle
Current Aging Science Are Circulating Monocytes as Microglia Orthologues Appropriate Biomarker Targets for Neuronal Diseases? (Supplementry Table)
Central Nervous System Agents in Medicinal Chemistry Editorial [Hot Topic: Sigma Receptor Research: Progress Towards Diagnostic and Therapeutic Uses of Sigma Ligands (Executive Guest Editor: Carmen Abate )]
Current Pharmaceutical Design Mesenchymal Stem Cells as Mediators of Neural Differentiation
Current Stem Cell Research & Therapy Autophagy and Cell Death in Caenorhabditis elegans
Current Pharmaceutical Design Gels and Jellies as a Dosage Form for Dysphagia Patients: A Review
Current Drug Therapy Recent Advances in Liver X Receptor Biology and Chemistry
Current Topics in Medicinal Chemistry Future Treatment for COPD: Targeting Oxidative Stress and its Related Signal
Recent Patents on Inflammation & Allergy Drug Discovery Nitric Oxide, Epileptic Seizures, and Action of Antiepileptic Drugs
CNS & Neurological Disorders - Drug Targets Receptor to Glutamate NMDA-Type: The Functional Diversity of the NR1 Isoforms and Pharmacological Properties
Current Pharmaceutical Design Gene Therapy and Cell Reprogramming For the Aging Brain: Achievements and Promise
Current Gene Therapy Functional Interactions of Tau and their Relevance for Alzheimers Disease
Current Alzheimer Research Current Overview of Inorganic Nanoparticles for the Treatment of Central Nervous System (CNS) Diseases
Current Nanomaterials Role of Sirtuins and Calorie Restriction in Neuroprotection: Implications in Alzheimers and Parkinsons Diseases
Current Pharmaceutical Design Gene Therapy Approaches to Ataxias
Current Gene Therapy Future Therapeutic Directions: New Medications and Insulin Delivery in a Changing World for Effective Diabetes Management
Current Drug Discovery Technologies