Abstract
Pathological folding and aggregation of the amyloid β-protein (Aβ) are widely perceived as central to understanding Alzheimers disease (AD) at the molecular level. Experimental approaches to study Aβ self-assembly are limited, because most relevant aggregates are quasi-stable and inhomogeneous. In contrast, simulations can provide significant insights into the problem, including specific sites in the molecule that would be attractive for drug targeting and details of the assembly pathways leading to the production of toxic assemblies. Here we review computer simulation approaches to understanding the structural biology of Aβ. We discuss the ways in which these simulations help guide experimental work, and in turn, how experimental results guide the development of theoretical and simulation approaches that may be of general utility in understanding pathologic protein folding and assembly.
Keywords: Alzheimer's disease, amyloid β-protein, computer simulations, coarse-grained protein model, protein folding, oligomer formation, fibril formation
Current Alzheimer Research
Title: Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly
Volume: 3 Issue: 5
Author(s): Brigita Urbanc, Luis Cruz, David B. Teplow and H. Eugene Stanley
Affiliation:
Keywords: Alzheimer's disease, amyloid β-protein, computer simulations, coarse-grained protein model, protein folding, oligomer formation, fibril formation
Abstract: Pathological folding and aggregation of the amyloid β-protein (Aβ) are widely perceived as central to understanding Alzheimers disease (AD) at the molecular level. Experimental approaches to study Aβ self-assembly are limited, because most relevant aggregates are quasi-stable and inhomogeneous. In contrast, simulations can provide significant insights into the problem, including specific sites in the molecule that would be attractive for drug targeting and details of the assembly pathways leading to the production of toxic assemblies. Here we review computer simulation approaches to understanding the structural biology of Aβ. We discuss the ways in which these simulations help guide experimental work, and in turn, how experimental results guide the development of theoretical and simulation approaches that may be of general utility in understanding pathologic protein folding and assembly.
Export Options
About this article
Cite this article as:
Urbanc Brigita, Cruz Luis, Teplow B. David and Stanley H. Eugene, Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly, Current Alzheimer Research 2006; 3 (5) . https://dx.doi.org/10.2174/156720506779025170
DOI https://dx.doi.org/10.2174/156720506779025170 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
High Content, Multi-Parameter Analyses in Buccal Cells to Identify Alzheimer’s Disease
Current Alzheimer Research S100b Induces Expression of Myoglobin in APβ Treated Neuronal Cells In Vitro: A Possible Neuroprotective Mechanism
Current Aging Science Chronic Administration of an Aglycosylated Murine Antibody of Ponezumab Does Not Worsen Microhemorrhages in Aged Tg2576 Mice
Current Alzheimer Research Edible Transgenic Plant Vaccines for Different Diseases
Current Pharmaceutical Biotechnology Tianeptine: A Novel Atypical Antidepressant that May Provide New Insights into the Biomolecular Basis of Depression
Recent Patents on CNS Drug Discovery (Discontinued) Immune Functions of Glia and Neurons in the Central Nervous System
Current Immunology Reviews (Discontinued) Role of Antioxidants, Essential Fatty Acids, Carnitine, Vitamins, Phytochemicals and Trace Elements in the Treatment of Diabetes Mellitus and its Chronic Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Curcumin-glucoside, A Novel Synthetic Derivative of Curcumin, Inhibits α-Synuclein Oligomer Formation: Relevance to Parkinson's Disease
Current Pharmaceutical Design Regenerative Potential of Stem Cells Derived from Human Exfoliated Deciduous (SHED) Teeth during Engineering of Human Body Tissues
Current Stem Cell Research & Therapy In Vitro Blood-Brain Barrier Models – Latest Advances and Therapeutic Applications in a Chronological Perspective
Mini-Reviews in Medicinal Chemistry Expression and Functions of LRP-2 in Central Nervous System: Progress in Understanding its Regulation and the Potential Use for Treatment of Neurodegenerative Diseases
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Metabolic Control of Glia-Mediated Neuroinflammation
Current Alzheimer Research Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review
Current Topics in Medicinal Chemistry Identification of Inflammatory, Metabolic, and Cell Survival Pathways Contributing to Cerebral Small Vessel Disease by Postmortem Gene Expression Microarray
Current Neurovascular Research The Impact of Angiotensin-Converting Enzyme Gene on Behavioral and Psychological Symptoms of Dementia in Alzheimer’s Disease
Current Alzheimer Research Editorial (Thematic Issue: Mitochondria and Subcellular Organelles as Treatment Targets Against Pathological Conditions)
Current Pharmaceutical Design Recent Developments in the Understanding and Treatment of Neurodegenerative Disorders Involving Protein Conformational Misfolding and Amyloid Formation
Medicinal Chemistry Reviews - Online (Discontinued) Quinoxaline Derivatives: Novel and Selective Butyrylcholinesterase Inhibitors
Medicinal Chemistry What is Tobacco Smoke? Sociocultural Dimensions of the Association with Cardiovascular Risk
Current Pharmaceutical Design Subcellular Analysis of the Platelet Proteome
Current Proteomics