Brain lipids in synaptic function and neurological disease : clues to innovative therapeutic strategies for brain disorders / Jacques Fantini, Nouara Yahi.

Format:

Book

Author/Creator:

Fantini, J. (Jacques), author.

Yahi, Nouara, 1964- author.

Contributor:

ScienceDirect (Online service)

Gail and Warren Lieberfarb Mental Health and Neuroscience Library Resources Fund.

Language:

English

Subjects (All):

Lipids.

Brain--Pathophysiology.

Brain.

Brain--physiology.

Medical Subjects:

Lipids.

Brain--physiology.

Physical Description:

1 online resource (398 pages)

polychrome

Place of Publication:

London ; San Diego, CA : Academic Press is an imprint of Elsevier, [2015]

System Details:

text file

Summary:

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 thousand 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 Alzhemer's, Creutzfeldt-Jakob's and Parkinson's. The authors conclude with new ideas that may drive innovative therapeutic strategies based on the knowledge of the role of lipids in brain disorders. Key Features: 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, Includes a companion website hosting additional content from the volume: Book jacket.

Contents:

1 Chemical Basis of Lipid Biochemistry 1

1.1 Introduction 1

1.2 Chemistry Backgroud 2

1.3 Molecular Interactions 3

1.4 Solubility in Water: What Is It? 4

1.5 Lipid Biochemistry 6

1.5.1 Definition 6

1.5.2 Biochemistry of Fatty Acids 7

1.5.3 Biochemistry of Saturated Fatty Acids 7

1.5.4 Biochemistry of Unsaturated Fatty Acids 9

1.5.5 Glycerolipids 11

1.5.6 Sphingolipids 14

1.5.7 Sterols 23

1.6 Biochemical Diversity of Brain Lipids 24

1.7 A Key Experiment: Lipid Analysis by Thin Layer Chromatography 25

References 26

2 Brain Membranes 29

2.1 Why Lipids are Different from all other Biomolecules 29

2.2 Role of Structured Water in Molecular Interactions 30

2.3 Lipid Self-assembly, a Water-Driven Process? 31

2.4 Lipid-Lipid Interactions: Why Such a High Specificity? 35

2.4.1 Melting Temperature of Lipids 36

2.4.2 The Molecular Shape of Lipids 38

2.5 Nonbilayer Phase and Lipid Dynamics 45

2.6 The Plasma Membrance of Glial Cells and Neurons: The Lipid Perspective 45

2.7 Key Experiments on Lipid Density 49

Reference 49

3 Lipid Metabolism and Oxidation in Neurons and Glial Cells 53

3.1 General Aspects of Lipid Metabolism 53

3.2 Cholesterol 56

3.3 Sphingolipids 61

3.3.1 Biosynthesis of Ceramide in the Endoplasmic Reticulum 62

3.3.2 Biosynthesis of Sphingomyelin in the Golgi 62

3.3.3 Glycosphingolipids 63

3.3.4 Sphingolipid Messengers 66

3.4 Phosphoinositides 70

3.5 Phosphatidic Acid 71

3.6 Endocannabinoids 74

3.7 Lipid Peroxidation 76

3.8 Key Experiment: Alzhemer's Disease, Cholesterol, and Statins: Where is the Link? 76

References 78

4 Variations of Brain Lipid 87

4.1 Brain Lipids: How to Bring Order to the Galaxy 87

4.2 Variations in Brain Cholesterol Content 89

4.2.1 Cholesterol and Aging 89

4.2.2 Brain Cholesterol and Neurodegenerative Deisease 92

4.3 Variations in Brain Ganglioside Content 93

4.3.1 Ceramide Variability 93

4.3.2 Sugar Head Group Variability 95

4.4 Variotions in Myelin Lipids 99

4.5 Impact of Nutrition on Brain Lipid Content 101

4.6 Key Experiment: The GM1/GM3 Balance and Alzheimer's Disease 103

References 103

5 A Molecular View of the Synapse 109

5.1 The Synapse: A Tripartite Entity? 109

5.2 Role of Gangliosides in Glutamate Clearence 110

5.3 Neurotransmitters and Their Receptors What Physicochemical Properties Reveal 113

5.4 A Dual Receptor Model for Serotonin 119

5.5 A Dual Receptor Model for Anandamide 121

5.6 Control of Synaptic Functions by Gangliosides 125

5.7 Control of Synaptic Functions by Cholesterol 127

5.8 Key Experiments: Debunking Myths in Neurosciences 129

References 130

6 Protein-Lipid Interactions in the Brain 135

6.1 General Aspects of Protein-Lipid Interactions 135

6.2 Annular Versus Nonannular lipids 137

6.3 Interactions Between Membrane Lipids and Cytoplasmic Domains 138

6.4 Interactions Between Membrane Lipids and Transmembrane Domains 139

6.4.1 Back to First Principles 139

6.4.2 Cholesterol-Binding Domains 140

6.4.3 Interaction of TM Domains with Sphingolipids 145

6.5 Interactions Between Membrane Lipids and Extracellular Domains 148

6.5.1 The Sphingolipid-Binding Domain (SBD) 148

6.5.2 Recognition of Membrane Cholesterol by extracellular Proteins 150

6.6 Chaperone effects 152

6.7 Conclusions 154

6.8 Key Experiment: The Langmuir Monolayer as a Universal Tool for the Study of Lipid-Protein Interactions 156

References 158

7 Lipid Regulation of Receptor Functions 163

7.1 Specific Lipid Requirement of Membrane Proteins 163

7.2 Nicotinic Acetylcholine Receptor 165

7.3 Cholesterol and Ganglioside-binding Domains in Serotonin Receptors 168

7.4 Cholesterol- and GalCer-binding Domains in Sigma-1 Receptors 172

7.5 GM1-Binding Domain in High-affinity NGF Receptor 173

7.6 Phosphoinositide Binding to Purinergic Receptros 174

7.7 Key Experiment: Transfection of Membrane Receptors: What About Lipids? 176

References 177

8 Common Mechanisms in Neurodegenerative Diseases 183

8.1 Amyloidosis: A Brief History 183

8.2 Protein Structure 184

8.3 Protein Folding 185

8.4 Intrinsically disordered Proteins(IDPs): The Dark Side of the Proteome 188

8.5 Lipid Rafts as Platforms for Amyloid Landing and Conversions 189

8.6 Amyloid Pores 190

8.7 Amyloid Fibrils 191

8.8 Common Molecular Mechanisms of Oligomerization and Aggregations 193

8.9 Therapeutic Strategies Based on Lipid Rafts 194

8.10 A Key Experiment: Common Structure of Amyloid Oligomers Implies Common Mechanism of Pahogenesis 196

References 198

9 Creutzfeld-Jakob Disease 201

9.1 Prion Diseases 201

9.2 PrP: Structural Features, Biological Functions, and Role in Neurological Diseases 202

9.3 The Mechanism or Prion Replication: A Great Intuition and an Intellectual Journey of an Imperturbable Logic 206

9.4 Role of Lipid Rafts in the conformational Plasticity of PrP 208

9.5 Conclusion of the Investigation: Who is Guilty, Who is Innocent? 218

9.6 Key Experiment: Adenine is a Minimal Aromatic compound that Self-aggregates in Water Through π-π Stacking Interactions 218

References 219

10 Parkinson's Disease 223

10.1 Parkinson's Disease and Synucleopathies 223

10.2 α-Synuclein 224

10.3 Intracellular α-Synuclein Binds to Synaptic Vesicles and Regulates Vesicle Trafficking, Docking, and Recycling 226

10.4 α-Synuclein is Secreted, Extracellular, and Taken up by Several Brain Cell Types 227

10.5 α-Synuclein: A Multifaceted Protein with Exceptional conformational Plasticity 228

10.6 How α-Synuclein Interacts with Membrane Lipids 231

10.7 Oligomerization of α-Synuclein into Ca²- Permeable Annular Channels 236

10.8 Electrophysiological Studies of Oligomeric α-Synuclein Channels 239

10.9 Cellular Targets for α-Synuclein in the Brain: The Lipid Connection 241

10.10 Conclusion of the Investigation: Who is Guilty, Who is Innocent? 243

10.11 Key Experiment: Pesticides and Animal Models of Parkinson's Disease 244

References 245

11 Alzheimer's Disease 253

11.1 Alzheimer's Disease: a Rapid Survey, from 1906 to 2014 253

11.2 The Amyloid Paradigm 255

11.3 The Calcium Hypothesis of Alzheimer's Disease 257

11.4 Amyloid Pores: β, α, or Both? 258

11.5 Cholesterol 260

11.6 GM1 263

11.7 Lipid Rafts: Matrix for APP Processing and Factory for Aβ Production 266

11.8 Gender-specific Mechanisms 268

11.9 Conclusions of the Inquiry 270

11.10 Key Experiment: A Blood-Based Test to Predict Alzheimer's Disease? 271

References 271

12 Viral and Bacterial Diseases 279

12.1 Overview of Brain Pathogens 279

12.2 Pathogen Traffic to the Brain 280

12.2.1 Rabies Virus: a Traveler to the Brain via Retrograde Axonal Routes 280

12.2.2 HIV: Strategies of Crossing the Blood-Brian Barrier 285

12.2.3 Listeria Monocytogenes 289

12.3 Overview of Brain Pathogens 293

12.3.1 Bacteria 293

12.3.2 Viruses 297

12.4 Key Experiment: What is a Virus Receptor? 301

References 303

13 A Unifying Theory 313

13.1 Why do we Need a Unifying Theory? 313

13.2 Bacteria, Viruses, and Amyloids converge at Brain Membranes 314

13.3 Glycosphingolipids and Cholesterol in Brain Membranes: "Un Pas De Deux" 315

13.4 Geometric Aspects of Glycolipid-Protein and Cholesterol Interactions 324

13.5 Why Two Lipid Receptors are Better Than One? 327

13.6 When Cholesterol Plays two Roles 328

13.7 Structural disorder as a Common Trait of Pathogenicity 329

13.8 Key Experiment: Probes to Study Cholesterol and/or Glycolipid-Dependent Mechanisms 330

References 332

14 Therapeutic Strategies for Neurodegenerative Diseases 337

14.1 Proteins Involved in Brain Diseases Considered as Infectious Proteins 337

14.2 How to Prevent the Interaction of Pathogenic Proteins with Brain Membranes 338

14.3 How to Prevent the Insertion of Pathogenic Proteins into Brain Membranes 340

14.4 How to Block Amyloid Pore Formation 340

14.5 A Universal Ganglioside-Binding Peptide 340

14.6 A Universal Squatter of cholesterol-Binding Sites 346

14.7 Could Anti-HIV Drugs Also be Considered for the Treatment of Neurodegenerative Deseases? 355

14.8 Conclusions 357

14.9 A Key Experiment: PAMPA-BBB, a Lipid-Based Model for the Blood-Brain Barrier 357

References 359.

Notes:

Includes bibliographical references and index.

Electronic reproduction. Amsterdam Available via World Wide Web.

Description based on online resource; title from digital title page (viewed on June 03, 2015).

Local Notes:

Acquired for the Penn Libraries with assistance from the Gail and Warren Lieberfarb Mental Health and Neuroscience Library Resources Fund.

ISBN:

9780128004920

0128004924

Publisher Number:

99963831573

Access Restriction:

Restricted for use by site license.