Neurodegenerative Disorders: Loss Of Function Through Gain Of Function (research And Perspectives In Alzheimer's Disease)

A fundamental change is occurring in the understanding of the major neurodegenerative disorders. Protein aggregation is a common emerging theme in diseases as diverse as Alzheimer's, Creutzfeld-Jakob, Parkinson's, and amyotrophic lateral sclerosis. If valid, then a small number of diagnostic and rational therapeutic strategies will emerge over the next few years, based on the common theme of modulation of the production, turnover and deposition of these aggregating proteins. The book provides insights into the cellular and animal models of these diseases, and how the molecular basis of neurodegeneration has become the preferred target of therapy. Front Matter....Pages I-XIV The Natural History of Alzheimer’s Disease: Minding the Gaps in Understanding the Mechanisms of Neurodegeneration....Pages 1-21 Mechanisms of Motor Neuron Death in ALS....Pages 23-40 Pathological Mechanisms in Huntington’s Disease and Other Polyglutamine Expansion Diseases....Pages 41-53 Prion Protein Biogenesis: Implications for Neurodegeneration....Pages 55-66 The Value of Transgenic Models for the Study of Neurodegenerative Diseases....Pages 67-86 Pathogenesis and Mechanism of Cerebral Amyloidosis in APP Transgenic Mice....Pages 87-95 Alzheimer’s Disease: Physiological and Pathogenetic Role of the Amyloid Precursor Protein (APP), its Aβ-Amyloid Domain and Free Aβ-Amyloid Peptide....Pages 97-117 The NEXT Step in Notch Processing and its Relevance to Amyloid Precursor Protein....Pages 119-128 The Putative Role of Presenilins in the Transmembrane Domain Cleavage of Amyloid Precursor Protein and Other Integral Membrane Proteins....Pages 129-140 ApoE Receptors in the Brain: Novel Signaling Pathways with Potential Relevance for Alzheimer’s Disease....Pages 141-148 Homeoprotein Intercellular Tansport: Mechanisms, Significance and Applications....Pages 149-158 Overexpression of APPL, a Drosophila APP Homologue, Compromises Microtubule Associated Axonal Transport and Promotes Synapse Formation....Pages 159-171 A Gain of Function of the Huntington’s Disease and Amyotrophic Lateral Sclerosis-Associated Genetic Mutations May Be a Loss of Bioenergetics....Pages 173-185 Back Matter....Pages 187-189