Molecular Biology of the Brain Book

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
5Neuro-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