Lipids and Cellular Membranes in Amyloid Diseases

Addressing one of the biggest riddles in current molecular cell biology, this ground-breaking monograph builds the case for the crucial involvement of lipids and membranes in the formation of amyloid deposits. Tying together recent knowledge from in vitro and in vivo studes, and built on a sound biophysical and biochemical foundation, this overview brings the reader up to date with current models of the interplay between membranes and amyloid formation. Required reading for any researcher interested in amyloid formation and amyloid toxicity, and possible avenues for the prevention or treatment of neurodegenerative disorders. From the contents: * Interactions of Alpha-Synuclein with Lipids * Interaction of hIAPP and its Precursors with Membranes * Amyloid Polymorphisms: Structural Basis and Significance in Biology and Molecular Medicine * The Role of Lipid Rafts in Alzheimer's Disease * Alzheimer's Disease as a Membrane-Associated Enzymopathy of Beta-Amyloid Precursor Protein (APP) Secretases * Impaired Regulation of Glutamate Receptor Channels and Signaling Molecules by Beta-Amyloid in Alzheimer's Disease * Membrane Changes in BSE and Scrapie * Experimental Approaches and Technical Challenges for Studying Amyloid-Membrane Interactions and more

Addressing one of the biggest riddles in current molecular cell biology, this ground-breaking monograph builds the case for the crucial involvement of lipids and membranes in the formation of amyloid deposits. Tying together recent knowledge from in vitro and in vivo studes, and built on a sound biophysical and biochemical foundation, this overview brings the reader up to date with current models of the interplay between membranes and amyloid formation.Required reading for any researcher interested in amyloid formation and amyloid toxicity, and possible avenues for the prevention or treatment of neurodegenerative disorders.From the contents:* Interactions of Alpha-Synuclein with Lipids* Interaction of hIAPP and its Precursors with Membranes* Amyloid Polymorphisms: Structural Basis and Significance in Biology and Molecular Medicine* The Role of Lipid Rafts in Alzheimer's Disease* Alzheimer's Disease as a Membrane-Associated Enzymopathy of Beta-Amyloid Precursor Protein (APP) Secretases* Impaired Regulation of Glutamate Receptor Channels and Signaling Molecules by Beta-Amyloid in Alzheimer's Disease* Membrane Changes in BSE and Scrapie* Experimental Approaches and Technical Challenges for Studying Amyloid-Membrane Interactionsand more

PrefaceINTERACTIONS OF ALPHA-SYNUCLEIN WITH LIPIDS AND ARTIFICIAL MEMBRANES MONITORED BY ESIPT PROBESIntroduction to Parkinson's Disease and Alpha-SynucleinStructural Biology of Alpha-SynucleinMethods for Studying AS-Lipid InteractionsAS-Lipid InteractionsInteractions of Monomeric AS with Artificial Membranes Monitored with ESIPT ProbesAggregation of AS and the Effects of Fatty Acids Monitored with ESIPT ProbesConcluding RemarksSTRUCTURAL AND FUNCTIONAL INSIGHTS INTO ALPHA-SYNUCLEIN-LIPID INTERACTIONSIntroductionInteration of Alpha-Synuclein with Model Membrane SystemsBiological SignificanceSURFACTANTS AND ALCOHOLS AS INDUCERS OF PROTEIN AMYLOID: AGGREGATION CHAPERONES OR MEMBRANE SIMULATORS?IntroductionAggregation in the Presence of SurfactantsPalimspsets of Future Functions: Cytotoxic Protein-Lipid ComplexesAggregation in Fluorinated Organic SolventsFrom Mimetics to the Real Thing: Aggregation on LipidsSummaryINTERACTION OF hlAPP AND ITS PRECURSORS WITH MODEL AND BIOLOGICAL MEMBRANESIntroductionResultsConclusionsAMYLOID POLYMORPHISMS: STRUCTURAL BASIS AND SIGNIFICANCE IN BIOLOGY AND MOLECULAR MEDICINEIntroductionOnly Generic Data Are Currently Available on the Structural Features of Amyloid OligomersThe Plasma Membrane Can Be a Primary Site of Amyloid Oligomer Generation and InteractionsOligomer/Fibril Polymorphism Can Underlie Amyloid CytotoxicityAmyloid Oligomers Grown Under Different Conditions Can Display Variable Cytotoxicity by Interacting in Different Ways with the Cell MembranesConclusionsINTRACELLULAR AMYLOID BETA: A MODIFICATION TO THE AMYLOID HYPOTHESIS IN ALZHEIMER'S DISEASEIntroductionEvidence for the Presence of Intracellular AmyloidSources of Intracellular AmyloidRelationship Between Intracellular and Extracellular AmyloidPrevention of Intracellular Amyloid ToxicityConcluding RemarksDisclosure StatementLIPID RAFTS PLAY A CRUCIAL ROLE IN PROTEIN INTERACTIONS AND INTRACELLULAR SIGNALING INVOLVED IN NEURONAL PRESERVATION AGINST ALZHEIMER'S DISEASELipid Rafts: Keys to Signaling Platforms in NeuronsEstrogen Receptors Are Part of Signaling Platforms in Neuronal RaftsRole of Lipid Raft ERAlpha-VDAC Interactions in Neuronal Preservation Against ABeta ToxicityDisruption of ERAlpha-VDAC Complex in AD BrainsFuture StudiesALZHEIMER'S DISEASE AS A MEMBRANE-ASSOCIATED ENZYMOPATHY OF BETA-AMYLOID PRECURSOR PROTEIN (APP) SECRETASESIntroductionIntramembrane-Cleaving Enzyme of Type I Membrane ProteinsAlcadein Processing by Gamma-Secretase in Alzheimer's DiseaseIMPAIRED REGULATION OF GLUTAMATE RECEPTOR CHANNELS AND SIGNALING MOLECULES BY BETA-AMYLOID IN ALZHEIMER'S DISEASEIntroductionAMPAR-Mediated Synaptic Transmission and Ionic Current are Impaired by ABetaCaMKII is Causally Involved in ABeta Impairment of AMPAR Trafficking and FunctionPIP2 Regulation of NMDAR Currents is Lost by ABetaThe Effect of AChE Inhibitor on NMDAR Response is Impaired in APP Transgenic MiceABeta Impairs PKC-Dependent Signaling and FunctionsConclusionMEMBRANE CHANGES IN BSE AND SCRAPIEPrion DiseasesThe Cellular Prion Protein (Prpc) and Conversion to Disease-Associated Prion Protein (PrPd)PrPd Accumulation in the Central Nervous System and Lymphatic TissuesAberrant Endocytosis and Trafficking of PrPd in Neurons and Tingible Body MacrophagesAbnormal Maturation Cycle and Immune Complex Trapping of Follicular Dendritic Cells in Lymphoid Germinal CentersMolecular Changes of Plasma Membranes Associated with PrPd AccumulationTransfer of PrPd Between CellsExtracellular Amyloid Form of PrPdStrain-Directed Effects of Prion InfectionConclusion and PerspectivesSummaryINTERACTION OF ALZHEIMER AMYLOID PEPTIDE WITH CELL SURFACES AND ARTIFICIAL MEMBRANESIntroductionComparison of the Neurotoxicity of Oligomeric and Fibrillar Alzheimer Amyloid PeptidesABeta Oligomerization at the Cell SurfaceCatalysis of ABeta Oligomerization by the Cell SrfaceType of ABeta Complexes that Form on the Cell SurfaceA