Abstract
Amyloidosis comprises a group of diseases characterized by the deposition of insoluble protein fibrils in specific organs and includes several serious medical disorders, such as Alzheimers disease, prion-associated transmissible spongiform encephalitis, and type II diabetes. Despite the structural dissimilarity between the soluble proteins and peptides, these fibrils exhibit similar morphologies under electron microscopy with a characteristic cross β- sheet pattern examined by x-ray fiber diffraction experiments. Many studies have revealed that each of these diseases is associated to a specific protein that is partially unfolded, misfolded, and aggregated. However, the detailed structures of the causative agents and the toxicity mechanisms are less known. This review summarizes recent studies in the conformational disorders leading to aggregation; including which proteins potentially cause conformational diseases, the aggregation mechanisms of these proteins, and recent researches on the conformational changes using advanced experiments or molecular dynamics simulations. Finally, current drug designs towards these protein conformational diseases are also discussed. It is believed that the advances in basic understanding of the mechanisms of conformational changes as well as biological functions of these proteins will shed light on the development and design of potential interfering compounds against amyloid formation associated with protein conformational diseases.
Keywords: Amyloidosis, Alzheimer's disease, Prion-associated transmissible spongiform encephalitis, Type II diabetes, Electron microscopy, X-ray fiber diffraction, Molecular dynamics simulations, Protein conformational disease
Current Drug Discovery Technologies
Title: Protein Conformational Diseases: From Mechanisms to Drug Designs
Volume: 3 Issue: 2
Author(s): Jin-Chung Lin and Hsuan-Liang Liu
Affiliation:
Keywords: Amyloidosis, Alzheimer's disease, Prion-associated transmissible spongiform encephalitis, Type II diabetes, Electron microscopy, X-ray fiber diffraction, Molecular dynamics simulations, Protein conformational disease
Abstract: Amyloidosis comprises a group of diseases characterized by the deposition of insoluble protein fibrils in specific organs and includes several serious medical disorders, such as Alzheimers disease, prion-associated transmissible spongiform encephalitis, and type II diabetes. Despite the structural dissimilarity between the soluble proteins and peptides, these fibrils exhibit similar morphologies under electron microscopy with a characteristic cross β- sheet pattern examined by x-ray fiber diffraction experiments. Many studies have revealed that each of these diseases is associated to a specific protein that is partially unfolded, misfolded, and aggregated. However, the detailed structures of the causative agents and the toxicity mechanisms are less known. This review summarizes recent studies in the conformational disorders leading to aggregation; including which proteins potentially cause conformational diseases, the aggregation mechanisms of these proteins, and recent researches on the conformational changes using advanced experiments or molecular dynamics simulations. Finally, current drug designs towards these protein conformational diseases are also discussed. It is believed that the advances in basic understanding of the mechanisms of conformational changes as well as biological functions of these proteins will shed light on the development and design of potential interfering compounds against amyloid formation associated with protein conformational diseases.
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Cite this article as:
Lin Jin-Chung and Liu Hsuan-Liang, Protein Conformational Diseases: From Mechanisms to Drug Designs, Current Drug Discovery Technologies 2006; 3 (2) . https://dx.doi.org/10.2174/157016306778108866
DOI https://dx.doi.org/10.2174/157016306778108866 |
Print ISSN 1570-1638 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6220 |
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Advancements in Computational Methods for Drug Design
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