Overview
- Editors:
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Ezio Giacobini
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School of Medicine, Southern Illinois University, Springfield, USA
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Robert E. Becker
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School of Medicine, Southern Illinois University, Springfield, USA
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Table of contents (81 papers)
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Nicotinic Agonists as Drugs for AD Treatment
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- Jeffrey A. Gray, Grigory A. Grigoryan, Chuly Lee, Stephen N. Mitchell, Helen Hodges
Pages 201-205
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- Roger L. Papke, Christopher M. de Fiebre, William Kem, Edwin M. Meyer
Pages 206-211
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- Paavo J. Riekkinen Jr., Minna K. Riekkinen, Jouni S. Sirviö
Pages 212-216
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Muscarinic Agonists: Preclinical and Clinical Approaches
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Front Matter
Pages 217-217
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- Abraham Fisher, Eliahu Heldman, David Gurwitz, Rachel Haring, Yishai Karton, Haim Meshulam et al.
Pages 219-223
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- Roy D. Schwarz, Michael J. Callahan, Robert E. Davis, Juan C. Jaen, William Lipinski, Charlotte Raby et al.
Pages 224-228
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- Harlan E. Shannon, Frank P. Bymaster, David O. Calligaro, Beverley Greenwood, Charles H. Mitch, John S. Ward et al.
Pages 229-233
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- N. C. Bodick, A. F. DeLong, P. L. Bonate, T. Gillespie, D. P. Henry, J. H. Satterwhite et al.
Pages 234-238
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Drugs to Enhance Acetylcholine Synthesis and Release
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Front Matter
Pages 245-245
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- Steven A. Farber, Barbara E. Slack, Enrico DeMicheli, Richard J. Wurtman, Roger M. Nitsch, John H. Growdon et al.
Pages 247-251
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- Robert Zaczek, Robert J. Chorvat, Richard A. Earl, S. William Tam
Pages 252-255
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Nootropic Drugs in AD Treatment
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Front Matter
Pages 257-257
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- Giancarlo Pepeu, Maria Grazia Giovannini, Ileana Marconcini Pepeu, Luciano Bartolini
Pages 259-264
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- Julian A. Gray, Jennifer A. Nagel, Roman Amrein, Giorgio Marini, Umberto Senin
Pages 270-274
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Neurotrophins, Growth Factors, and Neuroprotection in the Treatment of Alzheimer’s Disease
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Front Matter
Pages 275-275
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- Lars Svennerholm, Gino Toffano
Pages 284-289
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Excitatory Amino Acids, Ca++ Cellular Homeostasis, Nitric Oxide, and AD Treatment
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Front Matter
Pages 291-291
About this book
Since the apoE4 allele is a risk factor or susceptibility gene in late-onset familial and sporadic AD, the mechanism of disease expression may involve metabolic effects that are isoform specific. Isoform-specific interactions of apoE therefore become critical in the mechanism of AD pathogenesis. Detailed characterization of the binding of the apoE isoforms with proteins and peptides relevant to the pathology of the disease may be critical in understanding disease pathogenesis. These critical isoform-specific interactions of apoE may involve interactions with proteins and pep tides in the defining neuropathologic lesions of the disease, the neurofibrillary tangle and senile plaque. Other possible critical isoform-specific interactions include the mechanism of internalization, intracellular trafficking, and subsequent metabolism. In addition, differential post-translational modifications of apoE isoforms may determine differences in metabolism contributing to the pathogenesis of the disease. Oxidation of apoE may confer several isoform-specific, biochemically distinct properties. Since {3A peptide binds apoE in the lipoprotein binding domain of the protein and not in the receptor-binding domain, apoE could target bound {3A4 peptide to neurons via the LRP receptor. Internalization of the apoEI {3A peptide complex into the cell, by the same route as the apoE-containing lipoproteins, would result in incorporation into primary lysosomes and pH dependent dissociation. The demonstration of apoE in the cytoplasm of neurons, with isoform-specific interactions of apoE with the microtubule-binding protein tau demonstrated in vitro, suggest additional, testable hypotheses of disease pathogenesis.