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1. Tribute slide
2. Introduction
3. The brain and Alzheimer disease
4. What causes selective neuronal loss in AD?
5. The usual suspects
6. Tauist and BAPtist hypothesis of AD
7. Other hypothesis explaining AD
8. Clues to disease mechanism
9. Oxidative stress role in AD
10. Pathology and oxidative stress relationship in AD
11. Oxidative damage is the earliest event in AD
12. NFT and amyloid-beta
13. Oxidative stress induces tau phosphorylation
14. Stress-activated protein kinases and phospho-tau
15. Oxidative stress mediates amyloid-beta production
16. Amyloid-targeted approaches are unsuccessful
17. Is amyloid an antioxidant?
18. Amyloid-beta controls redox activity
19. Lipid peroxidation bound to amyloid-beta
20. Genetic mutations that cause AD
21. But what is the mechanism?
22. Genetic factors are related to oxidative stress
23. Therapeutics
24. Potential mechanism of ROS generation in AD
25. Oxidative modifications and macromolecules
26. Mitochondrial abnormalities: 5Kb-deleletion
27. Mitochondria/redox metal abnormalities
28. Oxidative damage directly correlates with mtDNA
29. Abnormal mitochondrial distribution in AD brains
30. Clinical investigation of AD brain
31. Mitochondria is not subject to oxidative damage
32. Role of mitochondria in oxidative modifications
33. Hydrogen peroxide generates oxidative radicals
34. In situ oxidation of 3,3' diaminobenzidine
35. Iron histochemistry
36. Redox active metals are also in cytoplasm
37. Controls lack endogenous redox active metals
38. Summary: oxidative stress
39. Predictions
40. Antioxidant diet is protective
41. Vitamin E diet and AD
42. Reducing the production of free radicals
43. Only one non-amyloid drug in phase III: 2010
44. Oxidative stress: cellular/animal models
45. Oxidative stress is necessary but not sufficient
46. Implication of cell mechanisms in AD
47. Fundamental mechanisms
48. Cell cycle related proteins in AD
49. CaMKII-MYC mice (1)
50. CaMKII-MYC mice (2)
51. DNA replication in CaMKII-MYC mice
52. Neurodegeneration in CaMKII-MYC mice (1)
53. Neurodegeneration in CaMKII-MYC mice (2)
54. Cognitive deficits in CaMKII-MYC mice
55. Cell cycle abnormalities: proliferation vs. cell death
56. Models are incomplete
57. Back to the drawing board?
58. Oxidative stress and cell cycle abnormalities
59. Which change occurs first?
60. Control cases (pre-Alzheimer?)
61. Early stages of AD disease signals
62. Two hit hypothesis
63. Are there more than two hits?
64. Targeting common mechanisms
65. Acknowledgments
66. Collaborators
67. Final quote

Topics Covered

• What causes selective neuronal loss in AD?
• Tauist and BAPtist hypothesis of AD
• Pathology and oxidative stress relationship
• NFT and amyloid-beta
• Stress-activated protein kinases and phospho-tau
• Amyloid-targeted approaches are unsuccessful
• Amyloid-beta controls redox activity
• Genetic factors are related to oxidative stress
• Therapeutics
• Potential mechanism of ROS generation
• Oxidative modifications and macromolecules
• Oxidative damage directly correlates with mtDNA
• Abnormal mitochondrial distribution in AD brains
• Iron histochemistry
• Antioxidant diet is protective
• Only one non-amyloid drug in phase III: 2010
• Oxidative stress is necessary but not sufficient
• CaMKII-MYC mice
• Oxidative stress and cell cycle abnormalities
• Early stages of AD disease signals

Links

Series:

• Alzheimer's Disease

Categories:

• Biochemistry
• Clinical Practice
• Neuroscience

Therapeutic Areas:

• Neurology

Talk Citation

Smith, M.A. (2011, June 12). Metabolic and biochemical alterations in Alzheimer's disease: facts and fictions [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/ERXS1787.
Export Citation (RIS)

Publication History

• Published on June 12, 2011

Financial Disclosures

• Prof. Mark A. Smith has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.