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1. Intro slide
2. The brain is vulnerable to oxidative stress
3. The chemistry of aging
4. Metals in the brain
5. Brain copper and iron rise in senescence
6. Metals mediate oxidation damage
7. Summary: Cu and Fe
8. Amyloid plaques and tangles
9. A-beta is cleaved from the APP
10. Alzheimer's Disease beta-amyloid (A-beta)
11. A-beta is a Cu/Zn metalloprotein
12. Zn & Cu precipitate A-beta rapidly and reversibly
13. Zinc, copper and iron in plaque
14. Zinc in plaque
15. Zinc and copper in the brain
16. Zinc in neocortex - electromicrography
17. Zinc transporter k/o inhibits A-beta deposition
18. Synaptic zinc fosters CAA
19. A-beta dimers in metal-chelated AD brain
20. A-beta is redox active
21. A-beta/Cu induces tyrosine radicals
22. Cu mediates A-beta catalytic activity
23. Peroxidative activity generates oxidized A-beta
24. A-beta-COX2 adducts are elevated in AD
25. Secondary consequences of H202 production
26. Amyloid plaques and oxidative damage in AD
27. Decreased Cu worsens amyloid
28. Pleiotropic effects of Cu levels
29. Does A-beta normally handle Cu?
30. Cu/Zn-A-beta forms hexamers
31. Cu accumulates in neurons lacking APP
32. Model for Alzheimer pathogenesis
33. Clioquinol
34. Effect of clioquinol on transgenic mice 1
35. Effect of clioquinol on transgenic mice 2
36. Clioquinol restores metal homeostasis
37. Effect of CQ upon ADAS-Cog
38. Effect of CQ upon plasma A-beta levels
39. Effect of CQ upon Zn levels
40. 125I-CQ in human brain
41. Copper-induced alpha-crystallin oxidation
42. Cu deficiency (Menkes ATP7A)
43. Iron trapping ameliorates MPTP
44. Summary

Topics Covered

• Production of reactive oxygen species (ROS)
• Chemical origin
• Generic mechanism of protein and transition metal combination
• Pathological protein aggregates
• Toxic ROS generation
• Role in etiology and tissue specificity of agedependent neurodegenerative diseases

Links

Series:

• Neurodegenerative Diseases

Categories:

• Clinical Practice
• Neuroscience

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on October 1, 2007
• Reviewed on August 13, 2020

Financial Disclosures

• Prof. Ashley Bush has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.