Neurodegenerative Diseases: Molecular And Cellular Mechanisms And Therapeutic Advances (gwumc Department Of Biochemistry And Molecular Biology Annual Spring Symposia)

Excitotoxicity and Selective Neuronal Vulnerability: Intracellular Signaling in Glutamate Excitotoxicity; I.J. Reynolds, et al. Modulation of Vesicular Glutamate Release during Anoxia; N. Hershkowitz, A.N. Katchman. A Model for the Expression of Different Glutamate Transporter Proteins from a RatAstrocytetype Glutamate Transporter Gene; R.S. Roginski. Glutamate Transporters: Molecular Mechanisms of Functional Alteration and Role in the Development of Excitotoxic Neuronal Injury; D. Trotti, et al. Neurodegenerative Disease and Oxidative Stress: Insights from an Animal Model of Parkinsonism; T.G. Hastings, M.J. Zigmond. Molecular and Genetic Risk Factors: In Vivo Biology of APP and Its Homologues; S.S. Sisodia, et al.. Lymphocyte Amyloid Precursor Protein mRNA Isoforms in Normal Aging and Alzheimer's Disease; R.P. Ebstein, et al. Differential Regulation of APP Secretion by Apolipoprotein E3 and E4; B. Wolozin, et al. Apolipoprotein EUptake Is Increased by Betaamylid Peptides and Reduced by Blockade of the LDL Receptor; U. Beffert, et al. Mutations of Human Cu, Zn Superoxide Dismutase Expressed in Transgenic Mice Cause Motor Neuron Disease; M.E. Gurney, et al. Cellular Metabolism: Functional Activation of Energy Metabolism in Nervous Tissue: Where and Why; L. Sokoloff, S. Takahashi. Bioenergetics in Oxidative Damage in Neurodegenerative Diseases; M.F. Beal. Is There a Relationship between Conditions Associated with Chronic Hypoxia, the Mitochondria, and Neurodegenerative Diseases such as Alzheimer's Disease? C.R. Merril, et al. Thiamine Deficiency as Model of Selective Neurodegeneration with Chronic Oxidative Deficits; N.Y. Calingasan, et al. Free Radicals and Oxidative Stress: The Protective Action of Nitronebased Free Radical Traps in Neurodegenerative Diseases; R.A. Floyd. Nitric Oxide Actions in the Nervous System; V.L. Dawson, T.M. Dawson. An Inflammatory Role for Nitric Oxide during Experimental Meningitis in the Rat; K.M.K. Boje. Oxidative Stress Plays a Role in the Pathogenesis of Familial Sporadic Amyotrophic Lateral Sclerosis; C. Bergeron, et al. Calcium Transportand Regulatory Proteins: Cysteine String Proteins: PresynapticFunction and Dysfunction; C.B. Gundersen, et al. AIDS Dementia as a Form of Excitotoxicity: Potential Therapy with NMDA Openchannel Blockers and Redox Congeners of Nitric Oxide; S.A. Lipton. Growth Regulation and Apoptosis: Detection of Single and Double Strand DNA Breaks during Excitotoxic or Apoptotic Neuronal-Cell Death; M. Didier, et al. Signaling for Survival: Potential Applications of Signaltransduction Therapies for Suppression of Apoptosis in the Nervous System; A.M. Tolkovsky. Ciliary Neurotrophic Factor (CNTF): Possible Implications in the Pathogenesis of Amyotrophic Lateral Sclerosis; R.W. Orrell, et al. Neuronal Differentiation of PC12 Cells in the Absence of Extracellular Matrix Adhesion Induces Apoptosis; H.W. Harris. 29 additional articles. Index. Front Matter....Pages i-xii Intracellular Signalling in Glutamate Excitotoxicity....Pages 1-7 Long-Term Expression of Proenkephalin and Prodynorphin in the Rat Brain after Systemic Administration of Kainic Acid — an in Situ Hybridization Study....Pages 9-18 Modulation of Vesicular Glutamate Release during Anoxia....Pages 19-27 A Model for the Expression of Different Glutamate Transporter Proteins from a Rat Astrocyte-Type Glutamate Transporter Gene....Pages 29-32 Glutamate Transporters: Molecular Mechanisms of Functional Alteration and Role in the Development of Excitotoxic Neuronal Injury....Pages 33-36 Neurodegenerative Disease and Oxidative Stress: Insights from an Animal Model of Parkinsonism....Pages 37-46 A Progressive Ballooning of Myelinated, TH-Positive Axons is Produced by MPTP in the Dog....Pages 47-53 HIV-1 Coat Protein GP120 Induces Neuronal Injury to Cultured Dopamine Cells....Pages 55-62 Platelets as Peripheral Model of Glutamate-Related Excitotoxicity in Parkinson’s Disease....Pages 63-68 Brainstem Motoneuron Cell Groups that die in Amyotrophic Lateral Sclerosis are Rich in the GLT-1 Glutamate Transporter....Pages 69-76 Progressive Neurodegeneration in Rat Brain after Chronic 3-VO or 2-VO....Pages 77-84 In Vivo Biology of APP and its Homologues....Pages 85-90 Lymphocyte Amyloid Precursor Protein mRNA Isoforms in Normal Aging and Alzheimer’s Disease....Pages 91-95 Differential Regulation of APP Secretion by Apolipoprotein E3 and E4....Pages 97-102 Apolipoprotein E Uptake is Increased by Beta-Amyloid Peptides and Reduced by Blockade of the LDL Receptor....Pages 103-108 The Non-Amyloid-β Component of Alzheimer’s Disease Plaque Amyloid: Comparative Analysis Suggests a Normal Function as a Synaptic Plasticizer....Pages 109-112 Mutations of Human Cu, Zn Superoxide Dismutase Expressed in Transgenic Mice Cause Motor Neuron Disease....Pages 113-122 Effect of the Kennedy Mutation of the Androgen Receptor on Gene Expression in Neuroblastoma Cells....Pages 123-131 Glutamate-Promoted Survival in Hippocampal Neurons: A Defect in Mouse Trisomy 16....Pages 133-139 RNA Message Levels in Normally Aging and in Alzheimer’s Disease(AD)-Affected Human Temporal Lobe Neocortex....Pages 141-145 Functional Activation of Energy Metabolism in Nervous Tissue: Where and Why....Pages 147-169 Bioenergetics in Oxidative Damage in Neurodegenerative Diseases....Pages 171-179 Is there a Relationship between Conditions Associated with Chronic Hypoxia, the Mitochondria, and Neurodegenerative Diseases, Such as Alzheimer’s Disease?....Pages 181-184 α-Ketoglutarate Dehydrogenase in Alzheimer’s Disease....Pages 185-191 Thiamine Deficiency as a Model of Selective Neurodegeneration with Chronic Oxidative Deficits....Pages 193-201 Metabolic Failure, Oxidative Stress, and Neurodegeneration Following Cerebral Ischemia and Reperfusion....Pages 203-209 Global Brain Ischemia and Reperfusion: Translation Initiation Factors....Pages 211-215 Batten Disease: A Typical Neuronal Storage Disease or a Genetic Neurodegenerative Disorder Characterized by Excitotoxicity?....Pages 217-224 Endogenous Amino Acid Profile during in Vitro Differentiation of Neural Stem Cells....Pages 225-234 The Protective Action of Nitrone-Based Free Radical Traps in Neurodegenerative Diseases....Pages 235-245 Nitric Oxide Actions in the Nervous System....Pages 247-262 An Inflammatory Role for Nitric Oxide during Experimental Meningitis in the Rat....Pages 263-273 Oxidative Stress Plays a Role in the Pathogenesis of Familial and Sporadic Amyotrophic Lateral Sclerosis....Pages 275-280 Modulation of the Mitochondrial Anti-Oxygen Radical Defense of Rat Astroglial Cells in Culture....Pages 281-283 Oxygen Radical-Mediated Oxidation of Serotonin: Potential Relationship to Neurodegenerative Diseases....Pages 285-297 Dopamine Covalently Modifies DNA in a Tyrosinase-Enhanced Manner....Pages 299-304 Brain [52FE]-Transferrin Uptake in Patients with Alzheimer’s Disease and Healthy Subjects: A Positron Emission Tomography (PET) Study....Pages 305-308 βAPP Metabolites, Radicals, Calcium, and Neurodegeneration: Novel Neuroprotective Strategies....Pages 309-329 Channel Formation by a Neurotoxic Beta Amyloid Peptide, Aβ25–35....Pages 331-336 Cysteine String Proteins: Presynaptic Function and Dysfunction....Pages 337-340 AIDS Dementia as a Form of Excitotoxicity: Potential Therapy with NMDA Open-Channel Blockers and Redox Congeners of Nitric Oxide....Pages 341-356 Calcium, AMPA/Kainate Receptors, and Selective Neurodegeneration....Pages 357-364 Diltiazem and MK-801 but not APV Act Synergistically to Protect Rat Hippocampal Slices against Hypoxic Damage....Pages 365-369 Intracellular Calcium Stores and Ischemic Neuronal Death....Pages 371-376 Calpain, a Catabolic Mediator in Spinal Cord Trauma....Pages 377-381 Detection of Single and Double Strand DNA Breaks during Excitotoxic or Apoptotic Neuronal Cell Death....Pages 383-392 Signalling for Survival: Potential Applications of Signal-Transduction Therapies for Suppression of Apoptosis in the Nervous System....Pages 393-399 Ciliary Neurotrophic Factor (CNTF): Possible Implications in the Pathogenesis of Amyotrophic Lateral Sclerosis....Pages 401-403 Neuronal Differentiation of PC12 Cells in the Absence of Extracellular Matrix Adhesion Induces Apoptosis....Pages 405-407 Excitable Membrane-Derived Lipid Mediators: Glutamate Release and Regulation of Gene Expression....Pages 409-425 Bcl-2 Protection of Mitochondrial Function Following Chemical Hypoxia/Aglycemia....Pages 427-434 Biochemical Characteristics of Oxygen-Induced and Low K + Medium-Induced Apoptotic Neuronal Death....Pages 435-437 Mechanisms of Selective Neuronal Vulnerability to 1-Methyl-4-Phenylpyridinium (MPP+) Toxicity....Pages 439-446 Potential Role of Hyperactivation of Signal Transduction Pathways in Alzheimer’s Disease: Protein Kinase C Regulates PHF-like Phosphorylation of Tau within Neuronal Cells....Pages 447-467 Back Matter....Pages 469-482 This book presents much of the exciting new information on mechanisms of neurodegenerative disorders that was presented at the XVth International Spring Symposium on Health Sciences at George Washington University in Washington, D.C. The organization of the symposium as weIl as the chapters within this book were based upon fundamental molecular and cellular mechanisms of neurodegeneration rather than upon different clinically defined disorders, in order to emphasize the commonality of cause rather than effect. The first part of the book is devoted to the relationships between selective vulnerability of different neuronal cell types to injury and their functional characteristics related to the transport, binding, and responses for excitatory amino acids, e.g., glutamate, as weIl as other neurotransmitters involved in toxicity. These relationships are studied in the context of neurodegeneration associated with several disorders including Parkinson's disease, amyotrophic lateral sclerosis (ALS), cerebral ischemia, and AIDS dementia. Part 11 emphasizes the role of amyloid proteins in neurodegeneration but also covers other molecular and genetic risk factors, e.g., expression of different apo lipoprotein isoforms and the involvement of abnormal superoxide dismutase in neuropathology. These topics are applied primarily to the aging brain, Alzheimer's disease, and ALS Proceedings of the Fifteenth Washington International Spring Symposium held at The George Washington University, Washington, D.C., May 15-17, 1995