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Brain Lipids in Synaptic Function and Neurological Disease
Clues to Innovative Therapeutic Strategies for Brain Disorders
1st Edition - May 12, 2015
Authors: Jacques Fantini, Nouara Yahi
Language: English
Hardback ISBN:9780128001110
9 7 8 - 0 - 1 2 - 8 0 0 1 1 1 - 0
eBook ISBN:9780128004920
9 7 8 - 0 - 1 2 - 8 0 0 4 9 2 - 0
Lipids are the most abundant organic compounds found in the brain, accounting for up to 50% of its dry weight. The brain lipidome includes several thousands of distinct bi…Read more
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Lipids are the most abundant organic compounds found in the brain, accounting for up to 50% of its dry weight. The brain lipidome includes several thousands of distinct biochemical structures whose expression may greatly vary according to age, gender, brain region, cell type, as well as subcellular localization. In synaptic membranes, brain lipids specifically interact with neurotransmitter receptors and control their activity. Moreover, brain lipids play a key role in the generation and neurotoxicity of amyloidogenic proteins involved in the pathophysiology of neurological diseases. The aim of this book is to provide for the first time a comprehensive overview of brain lipid structures, and to explain the roles of these lipids in synaptic function, and in neurodegenerative diseases, including Alzheimer’s, Creutzfeldt-Jakob’s and Parkinson’s. To conclude the book, the authors present new ideas that can drive innovative therapeutic strategies based on the knowledge of the role of lipids in brain disorders.
Written to provide a "hands-on" approach for readers
Biochemical structures explained with molecular models, and molecular mechanisms explained with simple drawings
Step-by-step guide to memorize and draw lipid structures
Each chapter features a content summary, up-to-date references for additional study, and a key experiment with an explanation of the technique
Neuroscience graduate students, post-doctoral fellows, experienced researchers new to neuroscience, and senior researchers that want technique updates
Dedication
About the Authors
Preface
Acknowledgments
Chapter 1: Chemical Basis of Lipid Biochemistry
Abstract
1.1. Introduction
1.2. Chemistry background
1.3. Molecular interactions
1.4. Solubility in water: what is it?
1.5. Lipid biochemistry
1.6. Biochemical diversity of brain lipids
1.7. A key experiment: lipid analysis by thin layer chromatography
Chapter 2: Brain Membranes
Abstract
2.1. Why lipids are different from all other biomolecules
2.2. Role of structured water in molecular interactions
2.3. Lipid self-assembly, a water-driven process?
2.4. Lipid–lipid interactions: why such a high specificity?
2.5. Nonbilayer phases and lipid dynamics
2.6. The plasma membrane of glial cells and neurons: the lipid perspective
2.7. Key experiments on lipid density
Chapter 3: Lipid Metabolism and Oxidation in Neurons and Glial Cells
Abstract
3.1. General aspects of lipid metabolism
3.2. Cholesterol
3.3. Sphingolipids
3.4. Phosphoinositides
3.5. Phosphatidic acid
3.6. Endocannabinoids
3.7. Lipid peroxidation
3.8. Key experiment: Alzheimer’s disease, cholesterol, and statins: where is the link?
Chapter 4: Variations of Brain Lipid Content
Abstract
4.1. Brain lipids: how to bring order to the galaxy
4.2. Variations in brain cholesterol content
4.3. Variations in brain ganglioside content
4.4. Variations in myelin lipids
4.5. Impact of nutrition on brain lipid content
4.6. Key experiment: the GM1/GM3 balance and Alzheimer’s disease
Chapter 5: A Molecular View of the Synapse
Abstract
5.1. The synapse: a tripartite entity?
5.2. Role of gangliosides in glutamate clearance
5.3. Neurotransmitters and their receptors: what physicochemical properties reveal
5.4. A dual receptor model for serotonin
5.5. A dual receptor model for anandamide
5.6. Control of synaptic functions by gangliosides
5.7. Control of synaptic functions by cholesterol
5.8. Key experiments: debunking myths in neurosciences
Chapter 6: Protein–Lipid Interactions in the Brain
Abstract
6.1. General aspects of protein–lipid interactions
6.2. Annular versus nonannular lipids
6.3. Interactions between membrane lipids and cytoplasmic domains
6.4. Interactions between membrane lipids and transmembrane domains
6.5. Interactions between membrane lipids and extracellular domains
6.6. Chaperone effects
6.7. Conclusions
6.8. Key experiment: the Langmuir monolayer as a universal tool for the study of lipid–protein interactions
Chapter 7: Lipid Regulation of Receptor Function
Abstract
7.1. Specific lipid requirement of membrane proteins
7.2. Nicotinic acetylcholine receptor
7.3. Cholesterol- and ganglioside-binding domains in serotonin receptors
7.4. Cholesterol- and GalCer-binding domains in sigma-1 receptors
7.5. GM1-binding domain in high-affinity NGF receptor
7.6. Phosphoinositide binding to purinergic receptors
7.7. Key experiment: transfection of membrane receptors: what about lipids?
Chapter 8: Common Mechanisms in Neurodegenerative Diseases
Abstract
8.1. Amyloidosis: a brief history
8.2. Protein structure
8.3. Protein folding
8.4. Intrinsically disordered proteins (IDPs): the dark side of the proteome
8.5. Lipid rafts as platforms for amyloid landing and conversions
8.6. Amyloid pores
8.7. Amyloid fibrils
8.8. Common molecular mechanisms of oligomerization and aggregation
8.9. Therapeutic strategies based on lipid rafts
8.10. A key experiment: common structure of amyloid oligomers implies common mechanism of pathogenesis
Chapter 9: Creutzfeldt–Jakob Disease
Abstract
9.1. Prion diseases
9.2. PrP: structural features, biological functions, and role in neurological diseases
9.3. The mechanism or prion replication: a great intuition and an intellectual journey of an imperturbable logic
9.4. Role of lipid rafts in the conformational plasticity of PrP
9.5. Conclusion of the investigation: who is guilty, who is innocent?
9.6. Key experiment: adenine is a minimal aromatic compound that self-aggregates in water through π–π stacking interactions
Chapter 10: Parkinson’s Disease
Abstract
10.1. Parkinson’s disease and synucleopathies
10.2. α-Synuclein
10.3. Intracellular α-synuclein binds to synaptic vesicles and regulates vesicle trafficking, docking, and recycling
10.4. α-Synuclein is secreted, extracellular, and taken up by several brain cell types
10.5. α-Synuclein: a multifaceted protein with exceptional conformational plasticity
10.6. How α-synuclein interacts with membrane lipids
10.7. Oligomerization of α-synuclein into Ca2+-permeable annular channels
10.8. Electrophysiological studies of oligomeric α-synuclein channels
10.9. Cellular targets for α-synuclein in the brain: the lipid connection
10.10. Conclusion of the investigation: who is guilty, who is innocent?
10.11. Key experiment: pesticides and animal models of Parkinson’s disease
Chapter 11: Alzheimer’s Disease
Abstract
11.1. Alzheimer’s disease: a rapid survey, from 1906 to 2014
11.2. The amyloid paradigm
11.3. The calcium hypothesis of Alzheimer’s disease
11.4. Amyloid pores: β, α, or both?
11.5. Cholesterol
11.6. GM1
11.7. Lipid rafts: matrix for APP processing and factory for Aβ production
11.8. Gender-specific mechanisms
11.9. Conclusions of the inquiry
11.10. Key experiment: a blood-based test to predict Alzheimer’s disease?
Chapter 12: Viral and Bacterial Diseases
Abstract
12.1. Overview of brain pathogens
12.2. Pathogen traffic to the brain
12.3. Overview of brain pathogens
12.4. Key experiment: what is a virus receptor?
Chapter 13: A Unifying Theory
Abstract
13.1. Why do we need a unifying theory?
13.2. Bacteria, viruses, and amyloids converge at brain membranes
13.3. Glycosphingolipids and cholesterol in brain membranes: “un pas de deux”
13.4. Geometric aspects of glycolipid–protein and cholesterol interactions
13.5. Why two lipid receptors are better than one?
13.6. When cholesterol plays two roles
13.7. Structural disorder as a common trait of pathogenicity
13.8. Key experiment: probes to study cholesterol and/or glycolipid-dependent mechanisms
Chapter 14: Therapeutic Strategies for Neurodegenerative Diseases
Abstract
14.1. Proteins involved in brain diseases considered as infectious proteins
14.2. How to prevent the interaction of pathogenic proteins with brain membranes
14.3. How to prevent the insertion of pathogenic proteins into brain membranes
14.4. How to block amyloid pore formation
14.5. A universal ganglioside-binding peptide
14.6. A universal squatter of cholesterol-binding sites
14.7. Could anti-HIV drugs also be considered for the treatment of neurodegenerative diseases?
14.8. Conclusions
14.9. A key experiment: PAMPA-BBB, a lipid-based model for the blood–brain barrier
Glossary
Subject Index
No. of pages: 398
Language: English
Edition: 1
Published: May 12, 2015
Imprint: Academic Press
Hardback ISBN: 9780128001110
eBook ISBN: 9780128004920
JF
Jacques Fantini
Jacques Fantini was born in France in 1960. He has over 30 years of teaching and research experience in biochemistry and neurochemistry areas. Since 1998, he is professor of biochemistry and honorary member of the ‘Institut Universitaire de France’. He has demonstrated the implication of glycolipids in the attachment and fusion of HIV-1 with the plasma membrane of target cells, and has published several important articles in this field. He is an active member of the research group ‘Molecular Interactions in Model and Biological Membrane Systems’ led by Nouara Yahi. This group is internationally recognized for studies of lipid-lipid and lipid-protein interactions pertaining to virus fusion, amyloid aggregation, oligomerization and pore formation. Together with Nouara Yahi, Jacques Fantini has discovered the universal sphingolipid-binding domain (SBD) in proteins with no sequence homology but sharing common structural features mediating sphingolipid recognition. The SBD is present in a broad range of infectious and amyloid proteins, revealing common mechanisms of pathogenesis in viral and bacterial brain infections, and in neurodegenerative diseases. His current research is focused on the molecular organization of the synapse in physiological and pathological conditions. Jacques Fantini is the author/co-author of 175 articles (PubMed), with 7500 citations and a H-index of 49. He has also published 4 patent applications. Jacques Fantini personal web site: https://jfantini.jimdo.com
Affiliations and expertise
Molecular Interactions in Model and Biological Membranes Laboratory, Faculty of Science and Technology, Marseille, France
NY
Nouara Yahi
Nouara Yahi was born in France in 1964. She has accumulated 25 years of fundamental research and teaching experience in virology and molecular biology areas. She has been a pioneer in the analysis of resistance mutations in patients with HIV infections, and has published several important articles in this field. She is currently professor of biochemistry at Aix-Marseille University and leader of the research group ‘Molecular Interactions in Model and Biological Membrane Systems’. This group is internationally recognized for studies of lipid-lipid and lipid-protein interactions pertaining to virus fusion, amyloid aggregation, oligomerization and pore formation. Together with her teammate Jacques Fantini, Nouara Yahi has discovered the universal sphingolipid-binding domain (SBD) in proteins with no sequence homology but sharing common structural features mediating sphingolipid recognition. The SBD is present in a broad range of infectious and amyloid proteins, revealing common mechanisms of pathogenesis in viral and bacterial brain infections, and in neurodegenerative diseases. Nouara Yahi is the author/co-author of 90 articles (PubMed), with 4400 citations and a H-index of 40. She has also published 5 patent applications.
Affiliations and expertise
Molecular Interactions in Model and Biological Membranes Laboratory, Faculty of Science and Technology, Marseille, France
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