Autophagy Dysfunction in Alzheimer's Disease and Dementia

1st Edition - August 20, 2022
Editors: Tadanori Hamano, Tatsuro Mutoh
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 8 9 9 0 6 - 2
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 8 9 9 1 4 - 7

Autophagy Dysfunction in Alzheimer’s Disease and Dementia provides an overview for researchers and clinicians on the mechanisms involved in protein degradation in Alzhei… Read more

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Autophagy Dysfunction in Alzheimer’s Disease and Dementia provides an overview for researchers and clinicians on the mechanisms involved in protein degradation in Alzheimer’s. The book discusses the implication of autophagy dysfunction in these diseases and how it causes degenerated proteins, including aggregated tau and aggregated amyloid protein. Other sections explores the possibilities of potential drug development through autophagy modulation, making this a great resource on the study of how autophagy dysfunction has been linked to the accumulation of misfolded proteins that cause death of neurons in Alzheimer’s and other neurodegenerative diseases.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Foreword
Preface
Acknowledgments
Section I: Degradation mechanisms of cells
Chapter 1: Degradation mechanisms of cells
Abstract
1: Neurons are highly polarized cells with the sophisticated trafficking system
2: Ubiquitin-proteasome system: UPS
3: Autophagy-endolysosomal system: APELS
4: Integration of cellular degradation systems
References
Section II: Lysosomes
Chapter 2: Lysosomes-neuronal degeneration in lysosomal storage disorders
Abstract
1: Lysosomes
2: Lysosomal storage diseases
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
4: Involvement of mitochondrial impairment in the onset of neurodegeneration in lysosomal storage diseases
5: Involvement of lysosomal impairment in the neuroinflammation
References
Section III: The autophagic pathways
Chapter 3: The autophagy pathway and its key regulators
Abstract
Acknowledgment
1: The autophagy machinery
2: Key regulators and signaling pathways of autophagy
3: Selective autophagy regulated by autophagic receptors
4: Concluding remarks
References
Section IV: Amyloid beta protein and autophagy
Chapter 4: Basics of amyloid β-protein in Alzheimer’s disease
Abstract
1: What is amyloid β?
2: Production and formation
3: Aggregation
4: Regulation of Aβ concentration in the brain
5: Decomposition and excretion
6: Relationship between Aβ and disease (including gene mutation)
7: Intervention strategy
References
Chapter 5: Molecular linkages among Aβ, tau, impaired mitophagy, and mitochondrial dysfunction in Alzheimer’s disease
Abstract
1: Introduction
2: Mitochondrial dysfunction
3: Defective mitophagy in AD
4: Mitochondrial dysfunction and defective mitophagy at the circuit and behavioral level
5: Future research
References
Chapter 6: Endocytosis in β-amyloid biology and Alzheimer’s disease
Abstract
1: Introduction
2: The flavors of endocytosis in the brain
3: The MO(F) of Aβ
4: Endocytosis in a phagocytic world
5: Adding a modifier, a new world for endocytosis in the AD brain
6: Endocytosis in a starry world
7: Exploiting endocytosis for therapeutic gain
8: Recycling full circle, a summary
References
Section V: Autophagy and tau protein
Chapter 7: Autophagy and tau protein
Abstract
Acknowledgments
1: Introduction
2: Tau protein
3: Autophagy
4: Disturbance of the autophagy-lysosome system in AD and related disorders
5: Tau degradation pathway
6: Mitophagy and tau
7: Diabetes, tau, and autophagy
8: Propagation of tau by the disruption of autophagy
9: Potential of autophagy modulators as a treatment for AD
10: Conclusion
References
Chapter 8: BAG3 promotes tau clearance by regulating autophagy and other vacuolar-dependent degradative processes
Abstract
Acknowledgments
1: Introduction
2: BAG3 protein
3: Summary
References
Chapter 9: Tau propagation and autophagy
Abstract
1: Introduction
2: Tau propagation mechanisms
3: Autophagic impairment promotes Tau aggregation
4: Pharmacological agents modulating Tau propagation
5: Conclusion
References
Section VI: Autophagy and pathology in Alzheimer’s disease
Chapter 10: Granulovacuolar degeneration in neurodegeneration
Abstract
Acknowledgment
1: Introduction
2: Neuropathological features of granulovacuolar degeneration (GVD) in neurons
3: What kind of organelle are GVBs?
4: GVB-like structures in oligodendroglia in multiple system atrophy
References
Chapter 11: Autophagy dysfunction in skeletal myopathies: Inclusion body myositis and Danon disease
Abstract
1: Autophagy and autophagic vacuoles
2: Autophagic vacuolar myopathy
3: Inclusion body myositis
4: Danon disease
5: Conclusion
References
Section VII: Autophagy and other disorders causing dementia
Chapter 12: Autophagy in Lewy body diseases and multiple system atrophy
Abstract
Acknowledgments
1: Introduction
2: Autophagy
3: Lewy body diseases
4: MSA
5: Conclusions
References
Chapter 13: Autophagy and Huntington’s disease
Abstract
1: Introduction
2: Macroautophagy in HD
3: Physiological function of Htt in autophagy
4: Autophagy: A therapeutic target
5: Conclusion
References
Section VIII: Drug discovery in Alzheimer’s disease by modulating autophagy
Chapter 14: Drug discovery in Alzheimer’s disease by regulating autophagy
Abstract
1: Introduction
2: Drugs that induce autophagy
3: Caspase activation and autophagy
4: Conclusion
References
Chapter 15: Drug discovery in Alzheimer’s disease using metal chelators: Warning toward their usage
Abstract
1: Introduction
2: Abnormal metals in AD patients
3: Clioquinol and SMON (subacute myelo-optico-neuropathy)
4: Conclusion
References
Chapter 16: Development of autophagy enhancers for Parkinson’s disease therapy
Abstract
Acknowledgment
1: Features of Parkinson’s disease
2: Current PD therapy
3: α-Synuclein accumulation in PD
4: Autophagy impairment in PD
5: Targeting macroautophagy for potential PD therapy
6: Targeting lysosome for potential PD therapy
7: Conclusions and future perspectives
References
Index

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Tadanori Hamano

Tatsuro Mutoh