Intracellular Traffic and Neurodegenerative Disorders (Research and Perspectives in Alzheimer's Disease)

This book explores the role of sub-cellular trafficking in the pathogenesis, treatment and prevention of neurodegenerative diseases. Recent findings point to faulty trafficking as contributing to the dysfunction and degeneration of neurons and neural circuits. Increasingly, research is targeting the mechanisms responsible and means to address them therapeutically. Many adult onset neurodegenerative diseases appear to arise from the accumulation of misfolded, neurotoxic peptides. This book investigates the ways in which sub-cellular trafficking pathways play a role both in the pathological accumulation of these misfolded proteins and in attempts to clear them. Because subcellular protein trafficking has an important role in the biology of neuronal function and survival, this also addresses how trophic factors maintain cell: cell interactions and how the underlying mechanisms may be compromised in neurodegenerative diseases. Examples where the use of such trophic factors may provide a way to modify neurodegenerative diseases are investigated. Front Matter....Pages i-xiv Amyloid Precursor Protein Sorting and Processing: Transmitters, Hormones, and Protein Phosphorylation Mechanisms....Pages 1-9 Intramembrane Proteolysis by γ-Secretase and Signal Peptide Peptidases....Pages 11-26 Axonal Transport and Neurodegenerative Disease....Pages 27-39 Simple Cellular Solutions to Complex Problems....Pages 41-57 Tau and Intracellular Transport in Neurons....Pages 59-70 Signaling Between Synapse and Nucleus During Synaptic Plasticity....Pages 71-85 Axonal Transport of Neurotrophic Signals: An Achilles' Heel for Neurodegeneration?....Pages 87-101 Membrane Trafficking and Targeting in Alzheimer's Disease....Pages 103-113 Huntington's Disease: Function and Dysfunction of Huntingtin in Axonal Transport....Pages 115-123 The Role of Retromer in Neurodegenerative Disease....Pages 125-140 Regulation of Endocytic Trafficking of Receptors and Transporters by Ubiquitination: Possible Role in Neurodegenerative Disease....Pages 141-155 The Sortilin-Related Receptor SORL1 is Functionally and Genetically Associated with Alzheimer's Disease....Pages 157-165 Regulation of Transport and Processing of Amyloid Precursor Protein by the Sorting Receptor SORLA....Pages 167-179 Back Matter....Pages 181-184