Abstract
Amyloid fibres are stable, persistent and highly ordered aggregates of mis-folded protein that accumulate in tissues and are a prominent feature of the pathology of a wide range of human diseases. The presumed role of amyloid as a causative factor of tissue damage is based largely on guilt by association. However, growing understanding of the nature of amyloid, its formation by a nucleated growth mechanism from destabilised and partially unfolded precursors and its persistence at sites of deposition has provided the foundation for the development of approaches to inhibit amyloid formation and enable its clearance. In spite of intensive study, our understanding of the detailed structure of amyloid itself remains incomplete although crossed-β structure is clearly a common constituent. On the other hand detailed structural understanding of transthyretin, β-secretase and serum amyloid P component is contributing to the design of small molecule compounds to target amyloid. Thyroxin mimetics stabilise the native tetrameric protein structure. β-secretase inhibitors will limit the production of the amyloidogenic Aβ1-42 polypeptide. Compounds that crosslink serum amyloid P component rapidly deplete the plasma and amyloid-βound pool of this protein. The efficacy of these compounds as drugs to prevent formation or enable removal of amyloid will provide a stringent test of the amyloid hypothesis of disease.
Keywords: Amyloid Diseases, tetrameric protein, serum amyloid
Current Drug Targets
Title: Perspectives for Drug Intervention in Amyloid Diseases
Volume: 5 Issue: 2
Author(s): Simon Kolstoe and Steve Wood
Affiliation:
Keywords: Amyloid Diseases, tetrameric protein, serum amyloid
Abstract: Amyloid fibres are stable, persistent and highly ordered aggregates of mis-folded protein that accumulate in tissues and are a prominent feature of the pathology of a wide range of human diseases. The presumed role of amyloid as a causative factor of tissue damage is based largely on guilt by association. However, growing understanding of the nature of amyloid, its formation by a nucleated growth mechanism from destabilised and partially unfolded precursors and its persistence at sites of deposition has provided the foundation for the development of approaches to inhibit amyloid formation and enable its clearance. In spite of intensive study, our understanding of the detailed structure of amyloid itself remains incomplete although crossed-β structure is clearly a common constituent. On the other hand detailed structural understanding of transthyretin, β-secretase and serum amyloid P component is contributing to the design of small molecule compounds to target amyloid. Thyroxin mimetics stabilise the native tetrameric protein structure. β-secretase inhibitors will limit the production of the amyloidogenic Aβ1-42 polypeptide. Compounds that crosslink serum amyloid P component rapidly deplete the plasma and amyloid-βound pool of this protein. The efficacy of these compounds as drugs to prevent formation or enable removal of amyloid will provide a stringent test of the amyloid hypothesis of disease.
Export Options
About this article
Cite this article as:
Kolstoe Simon and Wood Steve, Perspectives for Drug Intervention in Amyloid Diseases, Current Drug Targets 2004; 5 (2) . https://dx.doi.org/10.2174/1389450043490622
DOI https://dx.doi.org/10.2174/1389450043490622 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...read more
![](/images/wayfinder.jpg)
- 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
-
The Fibroblast Growth Factor 23: A New Player in the Field of Cardiovascular, Bone and Renal Disease
Current Vascular Pharmacology MICA Gene and Relevance to Immune Responses in Organ Transplants and Inflammatory, Tumoral and Autoimmune Diseases
Current Immunology Reviews (Discontinued) Executive Dyscontrol in Dementia, with Emphasis on Subcortical Pathology and the Role of Butyrylcholinesterase
Current Alzheimer Research Mental Training for Cognitive Improvement in Elderly People: What have We Learned from Clinical and Neurophysiologic Studies?
Current Alzheimer Research The Nrf2-ARE Pathway: A Valuable Therapeutic Target for the Treatment of Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Can Transcriptomics Cut the Gordian Knot of Amyotrophic Lateral Sclerosis?
Current Genomics New Tracers and New Perspectives for Molecular Imaging in Lewy Body Diseases
Current Medicinal Chemistry Identifying Dental Pulp Stem Cell as a Novel Therapeutic trategy for Digestive Diseases
Current Stem Cell Research & Therapy Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder
Current Neuropharmacology Growth Factors as Therapeutics for Diabetic Neuropathy
Current Drug Targets Predicting Progression from Cognitive Impairment to Alzheimer’s Disease with the Disease State Index
Current Alzheimer Research Mn-SOD and Chronic Inflammation of Gastric Mucosa
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Use of Stem Cells in Regenerative Medicine for Parkinson’s and Huntington’s Diseases
Current Medicinal Chemistry Renal Artery Stenting: Efficacy and Complications
Current Hypertension Reviews D-amino Acids as Novel Blood-based Biomarkers
Current Medicinal Chemistry Dietary Lipids and Alzheimer’s Disease
Current Alzheimer Research Emerging Use of Nanotechnology in the Treatment of Neurological Disorders
Current Pharmaceutical Design Vitiligo: Pathogenetic Hypotheses and Targets for Current Therapies
Current Drug Metabolism Novel Therapeutic Approaches to Autoimmune Demyelinating Disorders
Current Pharmaceutical Design Imaging Markers of Neurologic Damage in COVID-19: A Systematic Review
Current Medicinal Chemistry