Abstract
The aim of this review is to show how the challenging problem of understanding the physico-chemical basis of protein misfolding and aggregation which are at the origin of plaque formation in amyloid pathologies can be successfully investigated with a combination of modern spectroscopic techniques and advanced first principle numerical simulations. Within the vast group of diseases (more than 20) characterized by extra-cellular deposition of fibrillar material and generically called Amyloidosis, we shall focus on the Alzheimers disease, a progressive and devastating neurodegenerative pathology affecting an important fraction of the world aged population. Well identified peptides (the so called Aβ- peptides) undergo a misfolding process during the development of the disease. An important, but not yet fully elucidated, role appears to be played in these processes by transition metals (mainly copper and zinc) that have been observed to be present in large amounts in patients neurological plaques. Starting from this observation, a number of interesting results concerning the structural properties of the relevant metalpeptide binding site, emerging from the interplay between X-ray Absorption Spectroscopy experiments, and ab initio molecular dynamics simulations of the Car-Parrinello type will be reported and discussed.
Keywords: Aβ-peptide, metal ions, x-ray absorption spectroscopy, ab initio molecular dynamics
Current Alzheimer Research
Title: The Role of Metals in β -Amyloid Peptide Aggregation: X-Ray Spectroscopy and Numerical Simulations
Volume: 5 Issue: 6
Author(s): S. Morante
Affiliation:
Keywords: Aβ-peptide, metal ions, x-ray absorption spectroscopy, ab initio molecular dynamics
Abstract: The aim of this review is to show how the challenging problem of understanding the physico-chemical basis of protein misfolding and aggregation which are at the origin of plaque formation in amyloid pathologies can be successfully investigated with a combination of modern spectroscopic techniques and advanced first principle numerical simulations. Within the vast group of diseases (more than 20) characterized by extra-cellular deposition of fibrillar material and generically called Amyloidosis, we shall focus on the Alzheimers disease, a progressive and devastating neurodegenerative pathology affecting an important fraction of the world aged population. Well identified peptides (the so called Aβ- peptides) undergo a misfolding process during the development of the disease. An important, but not yet fully elucidated, role appears to be played in these processes by transition metals (mainly copper and zinc) that have been observed to be present in large amounts in patients neurological plaques. Starting from this observation, a number of interesting results concerning the structural properties of the relevant metalpeptide binding site, emerging from the interplay between X-ray Absorption Spectroscopy experiments, and ab initio molecular dynamics simulations of the Car-Parrinello type will be reported and discussed.
Export Options
About this article
Cite this article as:
Morante S., The Role of Metals in β -Amyloid Peptide Aggregation: X-Ray Spectroscopy and Numerical Simulations, Current Alzheimer Research 2008; 5 (6) . https://dx.doi.org/10.2174/156720508786898505
DOI https://dx.doi.org/10.2174/156720508786898505 |
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
-
Intraocular Inflammation and Systemic Immune-Mediated Diseases
Current Immunology Reviews (Discontinued) Knockdown of miR-124 Reduces Depression-like Behavior by Targeting CREB1 and BDNF
Current Neurovascular Research Assembly of the Asparagine- and Glutamine-Rich Yeast Prions into Protein Fibrils
Current Alzheimer Research Informal Caregiving for People with Dementia and Women’s Health: A Gender-based Assessment of Studies on Resilience
Current Women`s Health Reviews Agonist Replacement for Stimulant Dependence: A Review of Clinical Research
Current Pharmaceutical Design A Potential Contribution of Chemokine Network Dysfunction to the Depressive Disorders
Current Neuropharmacology Beyond the Reproductive Effect of Sex Steroids: Their Role During Immunity to Helminth Parasite Infections
Mini-Reviews in Medicinal Chemistry Collective Roles of Molecular Chaperones in Protein Degradation Pathways Associated with Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Monoclonal Antibodies: A Target Therapy for Multiple Sclerosis
Inflammation & Allergy - Drug Targets (Discontinued) Heart Rate Variability Indexes in Dementia: A Systematic Review with a Quantitative Analysis
Current Alzheimer Research Neuropharmacology of Vestibular System Disorders
Current Neuropharmacology Further Evaluation of the Neuropharmacological Determinants of the Antidepressant-Like Effects of Curcumin
CNS & Neurological Disorders - Drug Targets Cyclic Peptides that Govern Signal Transduction Pathways: From Prokaryotes to Multi-Cellular Organisms
Current Topics in Medicinal Chemistry D-Hormone Derivatives for the Treatment of Osteoporosis: From Alfacalcidol to Eldecalcitol
Mini-Reviews in Medicinal Chemistry Hyperammonemia Induced by Interaction of Valproate and Quetiapine
Current Drug Safety AVN-322 is a Safe Orally Bio-Available Potent and Highly Selective Antagonist of 5-HT6R with Demonstrated Ability to Improve Impaired Memory in Animal Models
Current Alzheimer Research Metabolic Functions of Myostatin and GDF11
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Editorial (Thematic Issue: Psychogeriatrics: An Interdisciplinary Approach)
Current Psychopharmacology Social Inequality and Substance Use and Problematic Gambling Among Adolescents and Young Adults: A Review of Epidemiological Surveys in Germany
Current Drug Abuse Reviews Neurotrophic Factor Treatment After Spinal Root Avulsion Injury
Central Nervous System Agents in Medicinal Chemistry