Essays in Biochemistry, Volume 33

Molecular Biology of the Brain

Buch | Hardcover

198 Seiten

2017
Princeton University Press (Verlag)
978-0-691-62885-1 (ISBN)

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The workings of the brain have long held a fascination for scientists. Yet, faced as they have been with the obvious anatomical and biochemical complexity of the brain, understanding its functions--more than superficially--has seemed an impossible goal. The authors of the essays in this volume, acknowledged experts in their specialties, have illustrated the power of molecular biology to dissect the molecular functioning of the brain. The volume has related essays on neurotransmitters and their receptors, aspects of neuronal development and neurodegeneration, the molecular biology of opiate action, and the concept of neuronal networks in the olfactory system. It continues with essays on some of the major healthcare problems that can be expected to yield to analysis by molecular genetical approaches--neurodegenerative and affective disorders such as schizophrenia, Alzheimer's disease, spongiform encephalopathies, prion diseases, and trinucleotide expansion disorders. The volume concludes first with an exciting account of how molecular biology is beginning to explain a phenomenon as complex as memory and, finally, a thought-provoking essay on future developments in the field.
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Preface xi Authors xiii Abbreviations xix 1 Molecular cues that guide the development of neural connectivity by Guy Tear Introduction 1 Netrins and their receptors 3 Sernaphorins/collapsins and their receptors 5 Eph receptor tyrosine kinases and their ligands, the ephrins 6 Extracellular matrix (ECM) and cell adhesion molecules 8 Guidance molecules at intermediate targets 9 Signal transduction of axon guidance signals 9 Future perspectives 10 Summary 11 References 11 2 Understanding neurotransmitter receptors: molecular biology-based strategies by Mark Wheatley Introduction 15 How many receptors? 16 Approaches to determining the structures and physiological functions of native neurotransmitter receptors 19 Receptor architecture and function 23 Future perspectives 25 Summary 26 References 26 3 Molecular analysis of neurotransmitter release by Giampietro Schiavo and Gudrun Stenbeck Introduction 29 SNARE proteins 31 Synaptotagmins as Ca2+ sensors at the synapse 35 Rab3 and neurotransmitter release 36 Phosphoinositide biosynthesis and turnover at the nerve terminal 37 Cytoskeleton and exocytosis 38 Proteins involved in synaptic vesicle enclocytosis 39 Perspectives 39 Summary 40 References 41 4 Mitochondria in the life and death of neurons by Samantha L. Budd and David G. Nicholls Introduction 43 Bioenergetic functions of brain mitochondria 44 Mitochondria and excitotoxicity 45 Mitochondrial hypotheses for neurodegenerative disorders 46 Mitochondria and programmed cell death 49 Perspectives 50 Summary 51 References 51 5 Neuro-regeneration: plasticity for repair and adaptation by Pico Caroni Introduction 53 Reactions of adult neurons to axotomy 55 Role of extrinsic factors in axonal regeneration 57 Role of intrinsic neuronal components in axonal regeneration 59 Factors that control nerve sprouting and synaptogenesis in the adult 60 Perspectives 62 Summary 63 References 63 6 A molecular basis for opiate action by Dominique Massotte and Brigitte L. Kieffer Introduction 65 The opioid system: discovery of a complex neurotransmitter system 67 Opioid receptors: first steps towards molecular mechanisms of opioid action 70 Recent approaches: from gene to function 74 Perspectives: an arduous march to therapeutics 75 Summary 76 References 76 7 Gases as neurotransmitters by Jane E. Haley Introduction 79 Why is everyone so interested in these gases? 80 NO and CO are formed by enzymes 80 What are the targets for NO and CO? 82 LTP in the hippocampus 83 Do NO and CO contribute to nociceptive signalling within the spinal cord? 88 Summary 89 References 90 8 Molecular biology of olfactory receptors by Yitzhak Pilpel, Alona Sosinsky and Doron Lancet Overview 93 Chemical detection in a probabilistic receptor repertoire 93 ORs belong to the G-protein-coupled receptor (GPCR) hyperfamily 94 Odorant complementarity-determining regions 96 Evolution of the OR repertoire 96 The biochemical cascade in olfactory signalling 96 Expressed OR proteins and their ligand specificity 98 Patterns of olfactory receptor expression and their transcriptional regulation 99 Olfactory bulb glomeruli represent ORs 101 Summary 102 References 102 9 Pathology and drug action in schizophrenia: insights from molecular biology by Philip G. Strange Introduction 105 Schizophrenia: the clinical picture 105 Changes in the brain in schizophrenia 106 Genetic linkage analysis of schizophrenia 108 Drug action in schizophrenia 109 Inverse agonism of anti-psychotic drugs 113 Conclusions 114 Summary 115 References 115 10 Genetics of Alzheimer's disease by Michael Hutton, Jordi Perez-Tur and John Hardy Introduction 117 Early-onset, autosomal dominant disease: the amyloid precursor protein (APP) and the presenilins 118 Effect of presenilin mutations on AB42(43) 123 Early-onset autosomal dominant AD 125 ApoE and other genetic risk factors for AD 126 Are there other Alzheimer genes, and what are they likely to be? 127 Summary 128 References 129 11 Use of brain grafts to study the pathogenesis of prion diseases by Adriano Aguzzi, Michael A. Klein, Christine Musahl, Alex J. Raeber, Thomas Blattler, Ivan Hegyi, Rico Frigg and Sebastian Brandner Introduction 133 Biological characteristics of mouse neuroectodermal grafts 135 Blood-brain barrier and brain grafts 135 Neurografts in prion research 137 Spread of prions in the CNS 138 Cells in the CNS that are affected by spongiform encephalopathies 141 Summary 145 References 145 12 Pathological mechanisms in Huntington's disease and other polyglutamine expansion diseases by Astrid Lunkes, Yvon Trottier and Jean-Louis Mandel Introduction 149 HD: clinical features 150 HD: neuropathology 154 Expansion mutation and genotype-phenotype correlations 154 Polyglutamine expansions in other neurodegenerative disorders 155 Nuclear inclusions and mechanisms of neurodegene ration 157 Summary 161 References 161 13 The matter of mind: molecular control of memory by Emily P. Huang and Charles F. Stevens Introduction 165 Synaptic basis of memory 166 LTP 167 Mutant mice, memory and LTP 170 Drosophila memory and cAMP 172 Long-term memory in Drosophila 173 CREB and mammalian memory 174 Perspectives 176 Summary 176 References 177 14 Future developments by Susan Greenfield Introduction 179 Why are there so many different neurotransmitters? 180 Why should neurotransmitters be released from outside of the classical synapse? 182 How can familiar transmitters have unpredictable actions? 185 How do transmitter actions relate to function? 186 How do transmitters relate to dysfunction? 187 Conclusions 189 Summary 189 References 190 Subject index 193

Erscheinungsdatum	01.03.2017
Reihe/Serie	Princeton Legacy Library
Verlagsort	New Jersey
Sprache	englisch
Maße	152 x 235 mm
Gewicht	482 g
Themenwelt	Naturwissenschaften ► Biologie ► Biochemie
ISBN-10	0-691-62885-8 / 0691628858
ISBN-13	978-0-691-62885-1 / 9780691628851
Zustand	Neuware