Cellular Mechanisms of Alzheimer's Disease: Neurodegenerative Diseases 2006

Contents......Page 4
Preface......Page 6
Six Years of Collaborative Alzheimer’s Disease Research in Germany......Page 8
The Microtubule-Associated Protein Tau......Page 12
Primary Structure of Tau and Prediction of Folding......Page 13
Global Features of Unfolded Proteins......Page 15
Long-Range Structure in Tau......Page 16
(Un)folding and Aggregation......Page 17
Conclusions......Page 19
References......Page 20
Introduction......Page 22
Materials and Methods......Page 23
MARK......Page 24
MARKK......Page 25
Outlook:Modes of MARK Regulation......Page 28
References......Page 31
Subcellular Trafficking of APP/APLPs......Page 33
Pathogenic Role of the APP Gene Family in Axonal Transport......Page 38
References......Page 39
Introduction......Page 42
Presenilin Function in C.elegans......Page 43
Suppressors and Enhancers of Presenilin in C. elegans......Page 44
References......Page 46
Abstract......Page 48
References......Page 52
Introduction......Page 54
APP/APLP Loss of Function Studies......Page 55
Roles of APP/APLP Proteins in the Formation of Neuromuscular Synapses and in Cortical Development......Page 56
Acknowledgement......Page 59
References......Page 60
Trafficking and Proteolytic Processing of APP......Page 62
Role of Glycosphingolipids in the Subcellular Transport of APP and the Generation of Abeta......Page 64
Role of BACE1 and BACE2 in APP Processing......Page 65
Role of GGA Proteins in the Proteolytic Processing of betaAPP......Page 66
References......Page 67
Introduction......Page 70
Identification of ADAM10 as an alpha-Secretase......Page 71
Transcriptional Regulation of the Human alpha-Secretase ADAM10 Gene......Page 72
Activation of alpha-Secretase via G Protein-Coupled Receptors......Page 73
Concluding Remarks......Page 74
References......Page 75
Proteolytic Processing of APP......Page 77
Expression Cloning Screen for Modifiers of APP Shedding......Page 78
Specificity of Identified cDNAs for APP Shedding......Page 79
Control of APP Shedding by Modulators of General Endocytosis......Page 80
APLP1 Modulates APP Shedding......Page 81
Conclusion......Page 82
References......Page 83
Abstract......Page 85
References......Page 88
Introduction......Page 90
Identification of gamma-Secretase......Page 91
Localization of gamma-Secretase and Its Cellular Site(s) of Activity......Page 92
Assembly of the gamma-Secretase Complex......Page 94
Acknowledgments......Page 95
References......Page 96
Introduction......Page 99
SPP-Like Proteins......Page 100
Nicalin (Nicastrin-Like Protein)......Page 102
References......Page 103
BACE Inhibitors......Page 105
Gamma-Secretase Inhibitors......Page 108
Outlook......Page 111
References......Page 112
Introduction: Abeta42 as a Therapeutic Target in Alzheimer’s Disease......Page 113
Gamma-Secretase Inhibition versus gamma-Secretase Modulations......Page 114
Abeta42-Lowering Compounds: In vitro Studies and Mechanism of Action......Page 115
Preclinical in vivo Studies and Clinical Trials with Abeta42-Lowering Compounds......Page 117
Acknowledgement......Page 118
References......Page 119
APP Processing......Page 120
Lipids – Risk Factor for AD......Page 121
The Role of APP and PSs in vivo......Page 122
Statins and Abeta-Mediated Cholesterol Downregulation......Page 123
Acknowledgement......Page 124
References......Page 125
Subject Index......Page 127