alzheimer's disease pathogenesis-core concepts, shifting paradigms and therapeutic targets

702 Pages·2011·34.69 MB·English

by  Intech Prepress 2

ALZHEIMER’S DISEASE
PATHOGENESIS-CORE
CONCEPTS, SHIFTING
PARADIGMS AND
THERAPEUTIC TARGETS

Edited by Suzanne De La Monte
Alzheimer’s Disease Pathogenesis-Core Concepts, Shifting Paradigms and
Therapeutic Targets
Edited by Suzanne De La Monte

Published by InTech
Janeza Trdine 9, 51000 Rijeka, Croatia

Copyright © 2011 InTech
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Image Copyright Carsten Erler, 2010. Used under license from Shutterstock.com

First published August, 2011
Printed in Croatia

A free online edition of this book is available at www.intechopen.com
Additional hard copies can be obtained from [email protected]

Alzheimer’s Disease Pathogenesis-Core Concepts, Shifting Paradigms and
Therapeutic Targets, Edited by Suzanne De La Monte
p. cm.
978-953-307-690-4
free online editions of InTech
Books and Journals can be found at
www.intechopen.com

Contents

Preface XI
Part 1 Overview 1
Chapter 1 Alzheimer´s Disease
– The New Actors of an Old Drama 3
Mario Álvarez Sánchez, Carlos A. Sánchez Catasús,
Ivonne Pedroso Ibañez, Maria L. Bringas and
Arnoldo Padrón Sánchez
Chapter 2 Pathophysiology of Late Onset Alzheimer Disease 21
Ahmet Turan Isik and M. Refik Mas
Part 2 Amyloid and Tau Mediated
Neurotoxicity and Neurodegeneration 29
Chapter 3 Expression and Cerebral Function of Amyloid
Precursor Protein After Rat Traumatic Brain Injury 31
Tatsuki Itoh, Motohiro Imano,
Shozo Nishida, Masahiro Tsubaki,
Shigeo Hashimoto, Akihiko Ito and Takao Satou
Chapter 4 Key Enzymes and Proteins in
Amyloid-Beta Production and Clearance 53
Cecília R A Santos, Isabel Cardoso and
Isabel Gonçalves
Chapter 5 Transporters in the Blood-Brain Barrier 87
Masaki Ueno, Toshitaka Nakagawa and
Haruhiko Sakamoto
Chapter 6 Contribution of Multivesicular Bodies
to the Prion-Like Propagation
of Lesions in Alzheimer’s Disease 107
Valérie Vingtdeux, Luc Buée and Nicolas Sergeant
VI Contents

Chapter 7 Pathological Stages of Abnormally
Processed Tau Protein During Its Aggregation
into Fibrillary Structures in Alzheimer’s Disease 131
Francisco García-Sierra, Gustavo Basurto-Islas,
Jaime Jarero-Basulto, Hugo C. Monroy-Ramírez,
Francisco M. Torres Cruz, Hernán Cortés Callejas,
Héctor M. Camarillo Rojas, Zdena Kristofikova,
Daniela Ripova, José Luna-Muñoz, Raúl Mena,
Lester I. Binder and Siddhartha Mondragón-Rodríguez
Chapter 8 Structure and Toxicity of the Prefibrillar Aggregation
States of Beta Peptides in Alzheimer’s Disease 151
Angelo Perico, Denise Galante and Cristina D’Arrigo
Chapter 9 Structural and Toxic Properties of
Protein Aggregates: Towards a Molecular
Understanding of Alzheimer's Disease 173
Lei Wang and Silvia Campioni
Part 3 Abnormalities in Signal Trandusction,
Neurotransmission, and Gene Regulation 195
Chapter 10 The Role of Glycogen Synthase
Kinase-3 (GSK-3) in Alzheimer’s Disease 197
Miguel Medina and Jesús Avila
Chapter 11 Pin1: A New Enzyme Pivotal for
Protecting Against Alzheimer’s Disease 223
Kazuhiro Nakamura, Suk Ling Ma and Kun Ping Lu
Chapter 12 Selectivity of Cell Signaling in the Neuronal Response
Based on NGF Mutations and Peptidomimetics in the
Treatment of Alzheimers Disease 243
Kenneth E. Neet, Sidharth Mahapatra, Hrishikesh M. Mehta
Chapter 13 Advances in MicroRNAs and
Alzheimer’s Disease Research 273
Francesca Ruberti, Silvia Pezzola and Christian Barbato
Part 4 Oxidative Stress, Reactive
Oxygen Species and Heavy Metals 295
Chapter 14 Role of Mitochondria in Alzheimer´s Disease 297
Genaro Genaro Gabriel Ortiz, Fermín Pacheco-Moisés,
José de Jesús García-Trejo, Roció E. González-Castañeda,
Miguel A. Macías-Islas, José A. Cruz-Ramos,
Irma E. Velázquez-Brizuela, Elva D. Árias Merino and
Alfredo Célis de la Rosa
Contents VII

Chapter 15 Oxidative Stress in Alzheimer’s Disease:
Pathogenesis, Biomarkers and Therapy 319
Alejandro Gella and Irene Bolea
Chapter 16 Impact of Oxidative - Nitrosative Stress
on Cholinergic Presynaptic Function 345
Stefanie A.G. Black and R. Jane Rylett
Chapter 17 Metals Involvement in
Alzheimer’s Disease Pathogenesis 369
Rosanna Squitti and Carlo Salustri
Chapter 18 Alzheimer’s Disease and Metal
Contamination: Aspects on Genotoxicity 403
P.D.L. Lima, M.C. Vasconcellos, R.C. Montenegro and R.R. Burbano
Part 5 Metabolic Derangements:
Glucose, Insulin, and Diabetes 435
Chapter 19 Glucose Metabolism and Insulin
Action in Alzheimer’s Disease Pathogenesis 437
Domenico Bosco, Massimiliano Plastino,
Antonio Spanò, Caterina Ermio and Antonietta Fava
Chapter 20 Insulin Resistance, Cognitive
Impairment and Neurodegeneration:
Roles of Nitrosamine Exposure, Diet and Lifestyles 459
Suzanne de la Monte, Ming Tong and Jack R. Wands
Chapter 21 The Relations Between the
Vitamins and Alzheimer Dementia 497
Emel Koseoglu
Part 6 Additional and Novel Concepts 519
Chapter 22 Hypotension in Subcortical Vascular Dementia,
a New Risk Factor – Wasn’t It Hypertension? 521
Rita Moretti, Francesca Esposito,
Paola Torre, Rodolfo M. Antonello and Giuseppe Bellini
Chapter 23 Autophagy-Derived Alzheimer’s Pathogenesis 539
Daijun Ling and Paul M. Salvaterra
Chapter 24 Plasmalogen Deficit: A New and Testable
Hypothesis for the Etiology of Alzheimer’s Disease 561
Paul L. Wood, M. Amin Khan,
Rishikesh Mankidy, Tara Smith and Dayan B. Goodenowe
VIII Contents

Chapter 25 Gangliosides as a Double-Edged
Swordin Neurodegenerative Disease 589
Akio Sekigawa, Masayo Fujita, Kazunari Sekiyama,
Yoshiki Takamatsu, Jianshe Wei and Makoto Hashimoto
Chapter 26 Structure Based 3D-QSAR
Studies on Cholinesterase Inhibitors 603
Zaheer ul Haq and Reaz Uddin
Part 7 Potential Therapeutic Strategies 633
Chapter 27 Tau Oligomers as Potential Drug
Target for Alzheimer Disease (AD) Treatment 635
Rakez Kayed
Chapter 28 In Silico Design of Preventive
Drugs for Alzheimer’s Disease 647
Arpita Yadav and Minakshi Sonker
Chapter 29 Protective Roles of the Incretin Hormones Glucagon-Like
Peptide-1 and Glucose-Dependent Insolinotropic
Polypeptide Hormones in Neurodegeneration 669
Christian Hölscher