Bioinorganic chemistry has a cross disciplinary approach, applying the principles of chemistry to biological systems. Metallochemistry of Neurodegeneration: Biological, Chemical and Genetic Aspects discusses the rapidly developing area of metals in the nervous system and their role in neurodegenerative disease, such as Alzheimer's, Parkinson's and prion diseases. Written by leading experts in their fields, each chapter combines elements of genetics, biochemistry and biological inorganic chemistry in its discussion. The book highlights the differences in pathologies of neurodegenerative diseases but also discusses the mechanistic similarities. Sections include: metal ions and prion diseases; metal ions and Alzheimer disease; manganese in brain functioning; metal involvement in Parkinson disease; Cu-Zn superoxide dismutase and familial amyotrophic lateral sclerosis. This book will appeal to both chemists and biologists at the postgraduate and research level.

Introduction	p. 1
General Model for Protein Misfolding, Aggregation, Amyloid Formation and Neurodegeneration	p. 1
Specificity of Molecular Mechanisms in Major Neurodegenerative Diseases	p. 2
Alzheimer Disease (AD)	p. 4
Parkinson Disease	p. 4
Amyotrophic Lateral Sclerosis	p. 6
Prions Diseases	p. 6
Models of Amyloid Seeding in Neurodegenerative Diseases	p. 8
References	p. 10
Blood-Brain Barrier and Roots of Entry of Metal Ions into the Brain. Metal Ion Transport and Distribution in the Brain	p. 12
General Features of Blood-Brain Barrier	p. 12
Iron and Aluminium	p. 14
Manganese	p. 17
Lead and Mercury	p. 19
The Olfactory Pathway of Metal Entry into the Brain	p. 20
Astroglia and Metal Accumulation	p. 20
References	p. 21
Metal Ion-Induced Redox Reactions, Oxidative Stress and Possible Impact on Neurodegeneration	p. 24
Metal Induced Production of ROS	p. 24
Nitric Oxide	p. 27
Oxidative Stress and Aging	p. 29
ROS, Protein Oxidation and Aberrant Protein Interactions	p. 29
Peroxidation of Lipids in Aging Brain	p. 33
Impact of Oxidative Stress on DNA	p. 33
ROS and Cell Death	p. 34
References	p. 35
Copper Metabolism in the Brain	p. 39
Introduction	p. 39
Models of Copper Metabolism	p. 40
Mammalian Copper Homeostasis	p. 44
Mammalian Cellular Copper Metabolism	p. 45
Neurodegenerative Diseases and Copper	p. 46
Wilson's and Menkes' Diseases	p. 46
Familial Amyotrophic Lateral Sclerosis	p. 51
Conclusions	p. 52
References	p. 53
Lithium, A Neuroprotective Element	p. 57
IMPase	p. 61
GSK-3	p. 71
References	p. 80
Neurotoxicity of Aluminium	p. 83
Neurochemistry of Aluminum	p. 83
Aluminum and the Etiology of Alzheimer's Disease	p. 92
References	p. 94
Manganese in the Brain Functioning	p. 97
Introduction	p. 97
Manganese Absorption	p. 98
Manganese Transport to the Brain	p. 99
Manganese Uptake in the Brain	p. 101
Proteins that Utilise Manganese	p. 103
Manganese Neurotoxicity	p. 110
Effects on Brain Function	p. 111
Neurological Disease Related to Manganese	p. 111
Conclusions	p. 113
References	p. 113
Alzheimer's Disease: Which Metal Now?	p. 117
Amyloid Precursor Protein	p. 118
Cleavage of APP and Formation of [Beta]-Amyloid	p. 120
Neurofibrillary Tangles	p. 122
Copper, APP and A[Beta]	p. 123
Metals and Alzheimer's Disease	p. 125
A Balance Between Copper and Zinc	p. 126
The Rise of Iron	p. 129
Any More Metals in Alzheimer's Disease?	p. 132
Coordination Chemistry of Metal Ions Interacting with APP	p. 132
References	p. 137
Prion Diseases and Redox Active Metals	p. 141
Introduction	p. 141
Cu-Binding to PrP[superscript c]	p. 147
Details of Cu[superscript 2+] Co-Ordination to Mammalian PrP[superscript c] and its Fragments	p. 149
Binding of Cu[superscript 2+] Ion by a Single Octapeptide Repeat Pro-His-Gly-Gly-Gly-Trp-Gly-Gln	p. 149
pH-Dependence of Cu[superscript 2+] Binding to Octapeptide Fragment	p. 150
Binding of Cu[superscript 2+] Ions to Dimeric and Tetrameric Octapeptide Fragments	p. 151
The Fifth and Sixth Binding Sites Located in N-Terminal Domain	p. 155
Binding of Cu[superscript 2+] and Other Metals to PrP91-126 Region Cu(II) Coordination to PrP106-126 (KTNMKHMAGAAAAGAVVGGLG)	p. 156
Involvement of His-96 in the Interaction of Cu(II) with the Neurotoxic Peptide Fragment	p. 158
The Comparison of the Binding Abilities of Octameric and Neurotoxic Regions Toward Cu[superscript 2+] Ions	p. 158
Cu[superscript 2+] Coordination to Chicken PrP	p. 160
Copper Mediated PrP Internalization	p. 162
Copper Transport	p. 166
PrP as an Antioxidant	p. 167
Manganese Binding	p. 170
Cell Death and Metals	p. 171
Direct Effects	p. 172
Indirect Effects	p. 173
Combined Effects	p. 173
Age Effects	p. 173
Metal Changes in TSEs	p. 174
Copper and Mutant Prions	p. 176
Conclusions	p. 176
References	p. 177
Are Metals Involved in Cu-Zn Superoxide Dismutase-Related Familial Amyotrophic Lateral Sclerosis	p. 182
References	p. 198
Parkinson's Disease: Any Role for Metals	p. 201
Introduction	p. 201
Cell Death in Parkinson's Disease	p. 202
Genetics of Parkison's Disease	p. 203
The Proteins Associated with Parkinson's Disease	p. 205
Parkin	p. 205
[Alpha]-Synuclein	p. 207
Metals in Parkinson's Disease	p. 211
Bioinorganic Chemistry in Parkinson Disease	p. 213
Binding of Copper Ions to [Alpha]-Synuclein and its Fragments	p. 214
Metal Ions and Catecholamines	p. 214
The Neuromelanin of Substantia Nigra and Metal Ions	p. 217
Conclusions	p. 218
References	p. 218
Chelating Agents in Metal Neurotoxicity	p. 223
Copper	p. 227
Lead	p. 230
Mercury	p. 232
Iron	p. 238
References	p. 242
Metal Complexes in the Brain Imaging and Diagnosis	p. 244
Gadolinium Compounds	p. 247
Monocrystalline Iron Oxide Nanocompounds	p. 249
Delivery of MRI Contrast Agents	p. 251
MRI Staining of the Hippocampal System	p. 263
Contrast Agents in Stem Cells Therapy	p. 266
Thallium Autometallography	p. 267
Targeting of Contrast Agents to AD Amyloid Plaques	p. 267
References	p. 274
Subject Index	p. 277
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