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.
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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 |
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