European Iron Club: Metal Based Neurodegenerative Diseases; Figure 11

The proposed sequence of events:

1.	Concentration of iron and copper increase in the cortex with aging. There is an overproduction of APP and Aβ in an attempt to suppress cellular metal-ion levels.
2.	Hypermetallation of Aβ occurs which may facilitate H₂O₂ production
3.	Hypermetallated Aβ reacts with H₂O₂ to generate oxidised and cross linked forms which are liberated from the membrane
4.	Soluble Aβ is released from the membrane and is precipitated by zinc which is released from the synaptic vesicles. Oxidised Aβ are the major components of the plaque deposits.
5.	Oxidised Aβ initiate microglia activation
6.	H₂O₂crosses cellular membranes to react with Cu and Fe, generate hydroxyl radicals which oxidise a variety of proteins and lipids.

Figure 11
Hypothetical model for the metallobiology of
Aβ in Alzheimer's disease. (from Bush 2003)

CONTENTS
Abstract
1.	Metals in Brain, Metal Transport, Storage and Homeostasis
2.	Oxidative Stress and Redox-Active Metal Ions
3.	Degradation of Cellular Proteins via Proteasomal System
4.	Parkinson's Disease
5.	Alzheimer's Disease
6.	Other Metal-Based Neurodegeneration Diseases
7.	Therapeutic Strategies
References
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