Autophagy Dysfunction in Alzheimer's Disease and Dementia

360 Pages·2022·19.295 MB·English

by  Tadanori Hamano, Tatsuro Mutoh

AUTOPHAGY
DYSFUNCTION
IN ALZHEIMER’S
DISEASE AND
DEMENTIA
This page intentionally left blank
AUTOPHAGY
DYSFUNCTION
IN ALZHEIMER’S
DISEASE AND
DEMENTIA
Edited by
TADANORI HAMANO
Associate Professor, Second Department of Internal
Medicine, Faculty of Medical Sciences, University of Fukui,
Fukui, Japan
Clinical Professor, Department of Neurology, University of
Fukui Hospital, Fukui, Japan
TATSURO MUTOH
Professor, Department of Neurology and Neuroscience,
Fujita Health University Hospital, Toyoake-City,
Aichi, Japan
Department of Internal Medicine Fujita Health University
Chubu International Airport Clinic, Tokoname-City,
Aichi, Japan
Academic Press is an imprint of Elsevier
125 London Wall, London EC2Y 5AS, United Kingdom
525 B Street, Suite 1650, San Diego, CA 92101, United States
50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States
The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom
Copyright © 2022 Elsevier Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopying, recording, or any information storage and
retrieval system, without permission in writing from the publisher. Details on how to seek
permission, further information about the Publisher’s permissions policies and our arrangements
with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency,
can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the
Publisher (other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical
treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in
evaluating and using any information, methods, compounds, or experiments described herein. In
using such information or methods they should be mindful of their own safety and the safety of
others, including parties for whom they have a professional responsibility.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors,
assume any liability for any injury and/or damage to persons or property as a matter of products
liability, negligence or otherwise, or from any use or operation of any methods, products,
instructions, or ideas contained in the material herein.
ISBN 978-0-323-89906-2
For information on all Academic Press publications
visit our website at https://www.elsevier.com/books-and-journals
Back cover image: Figure S2 (part B) reprinted from Bradlee L. Heckmann, Brett J.W. Teubner, Bart
Tummers, Emilio Boada-Romero, Lacie Harris, Mao Yang, Clifford S. Guy, Stanislav S. Zakharenko,
and Douglas R. Green. “LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates
Neurodegeneration in Murine Alzheimer’s Disease” in Cell, Vol 178, Issue 3, 25 July 2019, pp 536-551.
e14, with permission from Elsevier.
Publisher: Nikki Levy
Acquisitions Editor: Joslyn Chaiprasert-Paguio
Editorial Project Manager: Kristi Anderson
Production Project Manager: Maria Bernard
Cover Designer: Christian Bilbow
Typeset by STRAIVE, India
Dedication
This book is dedicated to Late Professor Masaru Kuriyama, University of
Fukui, Japan.
This page intentionally left blank
Contents
Contributors xiii
Foreword xvii
Preface xix
Acknowledgments xxi
SECTION I Degradation mechanisms of cells
1. Degradation mechanisms of cells 3
Asako Otomo and Shinji Hadano
1. Neurons are highly polarized cells with the sophisticated trafficking system 3
2. Ubiquitin-proteasome system: UPS 4
3. Autophagy-endolysosomal system: APELS 8
4. Integration of cellular degradation systems 18
References 19
SECTION II Lysosomes
2. Lysosomes-neuronal degeneration in lysosomal storage
disorders 25
Giulia Lunghi, Emma Veronica Carsana, Nicoletta Loberto,
Sandro Sonnino, and Massimo Aureli
1. Lysosomes 25
2. Lysosomal storage diseases 26
3. Impairment of lysosomal activity and alteration in the sphingolipid
composition of cell membranes: A possible link with the onset of
neuronal damage in LSD 31
4. Involvement of mitochondrial impairment in the onset
of neurodegeneration in lysosomal storage diseases 35
5. Involvement of lysosomal impairment in the neuroinflammation 38
References 40
SECTION III The autophagic pathways
3. The autophagy pathway and its key regulators 47
Tetsushi Kataura, Nobutaka Hattori, and Shinji Saiki
1. The autophagy machinery 47
2. Key regulators and signaling pathways of autophagy 49
vii
viii Contents
3. Selective autophagy regulated by autophagic receptors 58
4. Concluding remarks 61
Acknowledgment 62
References 62
SECTION IV Amyloid beta protein and autophagy
4. Basics of amyloid β-protein in Alzheimer’s disease 73
Azusa Sugimoto and Kenjiro Ono
1. What is amyloid β? 73
2. Production and formation 74
3. Aggregation 75
4. Regulation of Aβ concentration in the brain 78
5. Decomposition and excretion 78
6. Relationship between Aβ and disease (including gene mutation) 79
7. Intervention strategy 82
References 85
5. Molecular linkages among Aβ, tau, impaired mitophagy,
and mitochondrial dysfunction in Alzheimer’s disease 91
Tomas Schmauck-Medina, Thale D.J.H. Patrick-Brown, Shi-qi Zhang,
Alexandra Gilbert, and Evandro F. Fang
1. Introduction 91
2. Mitochondrial dysfunction 94
3. Defective mitophagy in AD 98
4. Mitochondrial dysfunction and defective mitophagy at the circuit
and behavioral level 101
5. Future research 103
Acknowledgments 103
Competing interests 104
References 104
6. Endocytosis in β-amyloid biology and Alzheimer’s disease 111
Bradlee L. Heckmann and Douglas R. Green
1. Introduction 111
2. The flavors of endocytosis in the brain 112
3. The MO(F) of Aβ 115
4. Endocytosis in a phagocytic world 117
Contents ix
5. Adding a modifier, a new world for endocytosis in the AD brain 120
6. Endocytosis in a starry world 124
7. Exploiting endocytosis for therapeutic gain 125
8. Recycling full circle, a summary 126
Acknowledgments 127
Disclosures 127
References 127
SECTION V Autophagy and tau protein
7. Autophagy and tau protein 135
Tadanori Hamano and Yoshinori Endo
1. Introduction 135
2. Tau protein 137
3. Autophagy 141
4. Disturbance of the autophagy-lysosome system in AD and related disorders 145
5. Tau degradation pathway 148
6. Mitophagy and tau 150
7. Diabetes, tau, and autophagy 151
8. Propagation of tau by the disruption of autophagy 151
9. Potential of autophagy modulators as a treatment for AD 153
10. Conclusion 153
Acknowledgments 154
References 154
8. BAG3 promotes tau clearance by regulating autophagy
and other vacuolar-dependent degradative processes 159
Changyi Ji, Heng Lin, and Gail V.W. Johnson
1. Introduction 159
2. BAG3 protein 161
3. Summary 167
Acknowledgments 169
References 169
9. Tau propagation and autophagy 173
Mohammad Nasir Uddin, Shotaro Shimonaka, and Yumiko Motoi
1. Introduction 173
2. Tau propagation mechanisms 174