Abstract
More and more evidence shows that Alzheimers and prion-related diseases belong to the family of conformational diseases characterized by protein self-association and tissue deposition as amyloid fibrils. Regardless of the nature of the protein constituent, all forms of amyloid are stable assemblies based on noncovalent interactions between subunits of crossed β-sheet structure. Understanding the mechanism and molecular details of the pathological conformational conversion of amyloidogenic proteins may be of importance to the development of approaches towards prevention and treatment of such diseases. We previously found that monoclonal antibodies (mAbs) interact at strategic sites where protein unfolding is initiated, thereby stabilizing the protein and preventing further precipitation. Indeed, site-directed mAbs raised against the N-terminal region of Alzheimers β-peptide (AβP) disaggregate AβP fibrils, restore peptide solubility and prevent its neurotoxic effects. Similarly, selected mAbs raised against the human prion peptide 106-126 modulate conformational changes occurring in the prion peptide exposed to aggregating conditions, preventing its aggregation and related neurotoxicity on cultivated neural-like cells. All these data and related procedures bring more attention to the immunological concept in the treatment of conformational diseases, and the recent performance of such antibodies in transgenic mice, as a model for human diseases, suggests the development of vaccination approaches against such diseases.
Keywords: Antibody, Conformational diseases, Amyloid, Immunomodulation, Conformation
Current Medicinal Chemistry
Title: Anti-Aggregating Antibodies, a New Approach Towards Treatment of Conformational Diseases
Volume: 9 Issue: 19
Author(s): Beka Solomon
Affiliation:
Keywords: Antibody, Conformational diseases, Amyloid, Immunomodulation, Conformation
Abstract: More and more evidence shows that Alzheimers and prion-related diseases belong to the family of conformational diseases characterized by protein self-association and tissue deposition as amyloid fibrils. Regardless of the nature of the protein constituent, all forms of amyloid are stable assemblies based on noncovalent interactions between subunits of crossed β-sheet structure. Understanding the mechanism and molecular details of the pathological conformational conversion of amyloidogenic proteins may be of importance to the development of approaches towards prevention and treatment of such diseases. We previously found that monoclonal antibodies (mAbs) interact at strategic sites where protein unfolding is initiated, thereby stabilizing the protein and preventing further precipitation. Indeed, site-directed mAbs raised against the N-terminal region of Alzheimers β-peptide (AβP) disaggregate AβP fibrils, restore peptide solubility and prevent its neurotoxic effects. Similarly, selected mAbs raised against the human prion peptide 106-126 modulate conformational changes occurring in the prion peptide exposed to aggregating conditions, preventing its aggregation and related neurotoxicity on cultivated neural-like cells. All these data and related procedures bring more attention to the immunological concept in the treatment of conformational diseases, and the recent performance of such antibodies in transgenic mice, as a model for human diseases, suggests the development of vaccination approaches against such diseases.
Export Options
About this article
Cite this article as:
Solomon Beka, Anti-Aggregating Antibodies, a New Approach Towards Treatment of Conformational Diseases, Current Medicinal Chemistry 2002; 9 (19) . https://dx.doi.org/10.2174/0929867023369141
DOI https://dx.doi.org/10.2174/0929867023369141 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Non Peptidic Urotensin II Antagonists: Perspectives for a New Class of Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry Induced Pluripotent Stem Cells as a Model for Accelerated Patient- and Disease-specific Drug Discovery
Current Medicinal Chemistry α-Synuclein Misfolding and Neurodegenerative Diseases
Current Protein & Peptide Science Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy
Anti-Cancer Agents in Medicinal Chemistry Prion Disease: Chemotherapeutic Strategies
Infectious Disorders - Drug Targets An Image-Based Biosensor Assay Strategy to Screen for Modulators of the microRNA 21 Biogenesis Pathway
Combinatorial Chemistry & High Throughput Screening Autophagy as a Molecular Target of Flavonoids Underlying their Protective Effects in Human Disease
Current Medicinal Chemistry Identifying S100B as a Biomarker and a Therapeutic Target For Brain Injury and Multiple Diseases
Current Medicinal Chemistry Antioxidants in Health, Disease and Aging
CNS & Neurological Disorders - Drug Targets Targeting Schistosome Histone Modifying Enzymes for Drug Development
Current Pharmaceutical Design Diversity and Variability of the Effects of Nicotine on Different Cortical Regions of the Brain. Therapeutic and Toxicological Implications
Central Nervous System Agents in Medicinal Chemistry A Simple and Reliable Approach for Assessing Anticancer Activity In Vitro
Current Medicinal Chemistry Pieces of the Complex Puzzle of Cancer Cell Energy Metabolism: An Overview of Energy Metabolism and Alternatives for Targeted Cancer Therapy
Current Medicinal Chemistry T Cell Costimulatory and Inhibitory Receptors as Therapeutic Targets for Inducing Anti-Tumor Immunity
Current Cancer Drug Targets Phenothiazines and Related Drugs as Multi Drug Resistance Reversal Agents in Cancer Chemotherapy Mediated by p-glycoprotein
Current Cancer Therapy Reviews NF-κB Signaling Pathway Inhibitors as Anticancer Drug Candidates
Anti-Cancer Agents in Medicinal Chemistry Perinatal Management of Fetal Tumors
Current Pediatric Reviews Anticancer Potential of Thiazole Derivatives: A Retrospective Review
Mini-Reviews in Medicinal Chemistry CHF5074 Protects SH-SY5Y Human Neuronal-like Cells from Amyloidbeta 25-35 and Tumor Necrosis Factor Related Apoptosis Inducing Ligand Toxicity In Vitro
Current Alzheimer Research Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors
Current Neuropharmacology