Abstract
Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer’s disease (AD), Parkinson disease (PD), Huntington’s disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naïve human scFv library, can recognize oligomers assembled from α-synuclein, amylin, insulin, Aβ40/42, prion peptide 106–126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of Aβ oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aβ levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.
Keywords: Alzheimer's disease, amyloid, immunotherapy, memory deficit, oligomer, single-chain variable fragment (scFv) antibody.
Current Alzheimer Research
Title:Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer’s Disease
Volume: 11 Issue: 1
Author(s): Min Zhao, Shao-wei Wang, Yu-jiong Wang, Ran Zhang, Ya-nan Li, Ya-jing Su, Wei-wei Zhou, Xiao-lin Yu and Rui-tian Liu
Affiliation:
Keywords: Alzheimer's disease, amyloid, immunotherapy, memory deficit, oligomer, single-chain variable fragment (scFv) antibody.
Abstract: Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer’s disease (AD), Parkinson disease (PD), Huntington’s disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naïve human scFv library, can recognize oligomers assembled from α-synuclein, amylin, insulin, Aβ40/42, prion peptide 106–126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of Aβ oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aβ levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.
Export Options
About this article
Cite this article as:
Zhao Min, Wang Shao-wei, Wang Yu-jiong, Zhang Ran, Li Ya-nan, Su Ya-jing, Zhou Wei-wei, Yu Xiao-lin and Liu Rui-tian, Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer’s Disease, Current Alzheimer Research 2014; 11 (1) . https://dx.doi.org/10.2174/15672050113106660176
DOI https://dx.doi.org/10.2174/15672050113106660176 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
- 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
-
Meningococcal Disease and Future Drug Targets
CNS & Neurological Disorders - Drug Targets Copper, An Ancient Remedy Returning to Fight Microbial, Fungal and Viral Infections
Current Chemical Biology Immunotherapy, Vascular Pathology, and Microhemorrhages in Transgenic Mice
CNS & Neurological Disorders - Drug Targets Pathogenesis of and Therapeutic Strategies to Ameliorate the Transthyretin Amyloidoses
Current Pharmaceutical Design Potential Relevance of Melatonin Against Some Infectious Agents: A Review and Assessment of Recent Research
Current Medicinal Chemistry Strategies to Diminish the Ab Load in Alzheimers Disease
Current Medicinal Chemistry - Central Nervous System Agents Future Targeted Disease Modifying Drugs for Alzheimer's Disease
Recent Patents on CNS Drug Discovery (Discontinued) Radiolabeled Organism-Specific Antibodies for Diagnosis and Therapy of Infections
Current Medical Imaging Mitochondrial Calcium Signaling as a Therapeutic Target for Alzheimer’s Disease
Current Alzheimer Research 4Aβ1-15-Derived Monoclonal Antibody Reduces More Aβ Burdens and Neuroinflammation than Homologous Vaccine in APP/PS1 Mice
Current Alzheimer Research Update on the Pharmacological Treatment of Alzheimers Disease
Current Neuropharmacology Exposure to Perinatal Infections and Bipolar Disorder: A Systematic Review
Current Molecular Medicine New Developments of Clinical Trial in Immunotherapy for Alzheimer's Disease
Current Pharmaceutical Biotechnology Vanutide Cridificar and the QS-21 Adjuvant in Japanese Subjects with Mild to Moderate Alzheimer’ s Disease: Results from Two Phase 2 Studies
Current Alzheimer Research Efficacy and Toxicity of Clioquinol Treatment and A-beta42 Inoculation in the APP/PSI Mouse Model of Alzheimer's Disease
Current Alzheimer Research On the Future Development of Optimally-Sized Lipid-Insoluble Systemic Therapies for CNS Solid Tumors and Other Neuropathologies
Recent Patents on CNS Drug Discovery (Discontinued) Advances in Chagas Disease Chemotherapy
Anti-Infective Agents in Medicinal Chemistry Heterogeneity in Cost-Effectiveness Analysis of Vaccination for Mild and Moderate Alzheimer’s Disease
Current Alzheimer Research Current Developments in Therapeutic and Diagnostic Strategies for Q Fever: Glimpses of Patent Analysis
Recent Patents on Anti-Infective Drug Discovery The Medical Potential of Antimicrobial Peptides from Insects
Current Topics in Medicinal Chemistry