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Alzheimer's Disease: Insights into Low Molecular Weight and Cytotoxic Aggregates from in Vitro and Computer Experiments
Molecular Basis of Amyloid-Beta Protein Aggregation and Fibril Formation
by Philippe Derreumaux
Hardback Book (464 Pages)
February 2013
Alzheimer's disease is the most common form of senile dementia, affecting more than 24 million people worldwide. It is characterised pathologically by abnormally high levels of brain lesions (senile plaques) in dead and dying neurons, and by elevated numbers of amyloid deposits in the walls of cerebral blood vessels. The major component of senile plaques is a small protein of 39-43 amino acids called amyloid. Thus far, no treatment has been shown to slow the progression of sporadic and familial Alzheimer's disease. A large body of evidence points to the early oligomers as the primary toxic species in Alzheimer's disease. A powerful strategy for developing pharmaceutical treatments against Alzheimer's is to elucidate the pathways of oligomer formation and determine the structures of the toxic aggregates. This book provides a panoramic view across recent in vitro and in vivo studies along with state-of-the-art computer simulations, designed to increase the readers' understanding of oligomerisation and fibril formation. At the same time, this book delves into the pathogenesis of familial and sporadic Alzheimer's disease at the atomic level of detail. Written by leading authors in their respective fields, this book will be valuable to all scientists working with Alzheimer's disease.
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•Cellular and In Vitro Aspects of Amyloid-Beta (Aâ) Aggregation: ◦Amyloid Hypothesis: Molecular and Cellular Aspects of Toxicity (Rakez Kayed and Cristian A Lasagna-Reeves)
◦Models of Wild-Type and Disease-Causing Mutant â-Amyloid Fibrils. Insights from Solid-State Nuclear Magnetic Resonance Spectroscopy (Stephen C Meredith)
◦Biophysical Characterization of Aâ Assembly (Eric Y Hayden and David B Teplow)
◦Coordination of Metal Ions to â-Amyloid Peptide: Impact on Alzheimer's Disease (Peter Faller, Giovanni La Penna, Christelle Hureau and Sara Furlan)
◦Amyloidogenesis, Neurogenesis, Learning, and Memory in Alzheimer's Disease: Lessons from Transgenic Mouse Models (Laure Verret and Claire Rampon)
◦Inhibitor Design Against Cytotoxic â-Amyloid Species (Andrew J Doig)

•Bioinformatics and Computer Simulations of Aâ Aggregation Under Various Environmental Conditions: ◦Kinetics of Amyloid Growth (Jessica Nasica-Labouze and Normand Mousseau)
◦Probing the Stability of Fibril and Tubular Species Using All-Atom Molecular Dynamics Simulations in Solution: Insight into Polymorphism (Yifat Miller, Buyong Ma and Ruth Nussinov)
◦Mechanisms of Growth of â-Amyloid Fibrils and Binding of Non-Steroidal Anti-Inflammatory Drug Ligands (Takako Takeda and Dmitri Klimov)
◦Exploring the Structures of â-Amyloid Oligomers in Aqueous Solution Using Coarse-Grained Protein Models (Yassmine Chebaro and Philippe Derreumaux)
◦Pathways of Amyloid Fibril Formation Using a Simplified Peptide Model (Riccardo Pellarin)
◦From Disordered Amyloid â-Proteins to Soluble Oligomers and Protofibrils Using Discrete Molecular Dynamics (Mark Betnel, Nikolay V Dokholyan and Brigita Urbanc)
◦Aâ Proteins–Lipid Membrane Interaction: Computational Simulation Study (Yuguang Mu)
◦Molecular Insights into the Assembly of â-Amyloid on Surfaces and Carbon Nanotubes (Guanghong Wei, Yin Luo and Zhaoming Fu)
◦Inhibiting Peptide and Protein Self-Aggregation: What Can Simulations Tell Us? (Joan-Emma Shea and Giorgio Colombo)
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