Lipids and Cellular Membranes in Amyloid Diseases

Currently at the department of Chemistry at Ben Gurion University, Israel, Raz Jelinek obtained his BSc in chemistry from the Hebrew University of Jerusalem, Israel, and his PhD from the University of California, Berkeley. He was a Cancer Research Institute post-doctoral fellow at the University of Pennsylvania and a Visiting Professor at the Department of Chemical and Biomolecular Engineering at Johns Hopkins University. Professor Jelinek has over 90 scientific publications and 10 patents to his name, and has received several scientific awards, including the Roger-Siegel-Brown Award of the Israeli Academy of Science and the Ruth L. Kirschstein National Research Service Award of the National Institutes of Health, USA.

Preface
INTERACTIONS OF ALPHA-SYNUCLEIN WITH LIPIDS AND ARTIFICIAL MEMBRANES MONITORED BY ESIPT PROBES
Introduction to Parkinson's Disease and Alpha-Synuclein
Structural Biology of Alpha-Synuclein
Methods for Studying AS-Lipid Interactions
AS-Lipid Interactions
Interactions of Monomeric AS with Artificial Membranes Monitored with ESIPT Probes
Aggregation of AS and the Effects of Fatty Acids Monitored with ESIPT Probes
Concluding Remarks
STRUCTURAL AND FUNCTIONAL INSIGHTS INTO ALPHA-SYNUCLEIN-LIPID INTERACTIONS
Introduction
Interation of Alpha-Synuclein with Model Membrane Systems
Biological Significance
SURFACTANTS AND ALCOHOLS AS INDUCERS OF PROTEIN AMYLOID: AGGREGATION CHAPERONES OR MEMBRANE SIMULATORS?
Introduction
Aggregation in the Presence of Surfactants
Palimspsets of Future Functions: Cytotoxic Protein-Lipid Complexes
Aggregation in Fluorinated Organic Solvents
From Mimetics to the Real Thing: Aggregation on Lipids
Summary
INTERACTION OF hlAPP AND ITS PRECURSORS WITH MODEL AND BIOLOGICAL MEMBRANES
Introduction
Results
Conclusions
AMYLOID POLYMORPHISMS: STRUCTURAL BASIS AND SIGNIFICANCE IN BIOLOGY AND MOLECULAR MEDICINE
Introduction
Only Generic Data Are Currently Available on the Structural Features of Amyloid Oligomers
The Plasma Membrane Can Be a Primary Site of Amyloid Oligomer Generation and Interactions
Oligomer/Fibril Polymorphism Can Underlie Amyloid Cytotoxicity
Amyloid Oligomers Grown Under Different Conditions Can Display Variable Cytotoxicity by Interacting in Different Ways with the Cell Membranes
Conclusions
INTRACELLULAR AMYLOID BETA: A MODIFICATION TO THE AMYLOID HYPOTHESIS IN ALZHEIMER'S DISEASE
Introduction
Evidence for the Presence of Intracellular Amyloid
Sources of Intracellular Amyloid
Relationship Between Intracellular and Extracellular Amyloid
Prevention of Intracellular Amyloid Toxicity
Concluding Remarks
Disclosure Statement
LIPID RAFTS PLAY A CRUCIAL ROLE IN PROTEIN INTERACTIONS AND INTRACELLULAR SIGNALING INVOLVED IN NEURONAL PRESERVATION AGINST ALZHEIMER'S DISEASE
Lipid Rafts: Keys to Signaling Platforms in Neurons
Estrogen Receptors Are Part of Signaling Platforms in Neuronal Rafts
Role of Lipid Raft ERAlpha-VDAC Interactions in Neuronal Preservation Against ABeta Toxicity
Disruption of ERAlpha-VDAC Complex in AD Brains
Future Studies
ALZHEIMER'S DISEASE AS A MEMBRANE-ASSOCIATED ENZYMOPATHY OF BETA-AMYLOID PRECURSOR PROTEIN (APP) SECRETASES
Introduction
Intramembrane-Cleaving Enzyme of Type I Membrane Proteins
Alcadein Processing by Gamma-Secretase in Alzheimer's Disease
IMPAIRED REGULATION OF GLUTAMATE RECEPTOR CHANNELS AND SIGNALING MOLECULES BY BETA-AMYLOID IN ALZHEIMER'S DISEASE
Introduction
AMPAR-Mediated Synaptic Transmission and Ionic Current are Impaired by ABeta
CaMKII is Causally Involved in ABeta Impairment of AMPAR Trafficking and Function
PIP2 Regulation of NMDAR Currents is Lost by ABeta
The Effect of AChE Inhibitor on NMDAR Response is Impaired in APP Transgenic Mice
ABeta Impairs PKC-Dependent Signaling and Functions
Conclusion
MEMBRANE CHANGES IN BSE AND SCRAPIE
Prion Diseases
The Cellular Prion Protein (Prpc) and Conversion to Disease-Associated Prion Protein (PrPd)
PrPd Accumulation in the Central Nervous System and Lymphatic Tissues
Aberrant Endocytosis and Trafficking of PrPd in Neurons and Tingible Body Macrophages
Abnormal Maturation Cycle and Immune Complex Trapping of Follicular Dendritic Cells in Lymphoid Germinal Centers
Molecular Changes of Plasma Membranes Associated with PrPd Accumulation
Transfer of PrPd Between Cells
Extracellular Amyloid Form of PrPd
Strain-Directed Effects of Prion Infection
Conclusion and Perspectives
Summary
INTERACTION OF ALZHEIMER AMYLOID PEPTIDE WITH CELL SURFACES AND ARTIFICIAL MEMBRANES
Introduction
Comparison of the Neurotoxicity of Oligomeric and Fibrillar Alzheimer Amyloid Peptides
ABeta Oligomerization at the Cell Surface
Catalysis of ABeta Oligomerization by the Cell Srface
Type of ABeta Complexes that Form on the Cell Surface
Association of Alzheimer Amyloid Peptides with Lipid Particles
Future Directions
EXPERIMENTAL APPROACHES AND TECHNICAL CHALLENGES FOR STUDYING AMYLOID-MEMBRANE INTERACTIONS
Introduction
Unilamellar Vesicles and Micelles
Black Lipid Membranes
Langmuir Monolayers
Solid-Supported Bilayers
Other Techniques
Challenges and Future Work












Interactions of Alpha-Synuclein with Lipids and Artificial Membranes Monitored by ESPIT Probes
Structural and Functional Insights Into Alpha-Synuclein Lipid Interactions
Surfactants and Alcohols as Inducers of Protein Amyloid: Aggregation Chaperones or Membrane Simulators?
Interaction of hIAPP and its Precursors with Model and Biological Membranes
Amyloid Polymorphisms: Structural Basis and Significance in Biology and Molecular Medicine
Intracellular Amyloid Beta: A Modification to Amyloid Hypothesis in Alzheimer's Disease
Lipid Rafts Play a Crucial Role in Protein Interactions and Intracellular Signaling Involved in Neuronal Preservation Against Alzheimer's Disease
Alzheimer's Disease as Membrane-Associated Enzymopathies of APP Secretases
Impaired Regulation of Glutamate Receptor Channels and Signaling Molecules by Beta-Amyloid in Alzheimer's Disease
Membrane Changes in BSE and Scapie
Interaction of Alzheimer Amyloid Peptide with Cell Surfaces and Artificial Membranes
Experimental Approach and Technical Challenges for Studying Amyloid-Membrane Interactions

"In general, this is a very informative and comprehensive book for anyone interested in amyloidogenic diseases and the role of membranes and lipids in the formation of amyloidogenic protein structures and toxic consequences; a field of rapidly increasing interest." (ChemMedChem, 2011)