• Introduction to Free Radicals and Oxidative Stress
• 57 min
  1. Introduction to free radicals and the oxygen paradox: oxidative stress in biology, aging & disease

  • Prof. Kelvin Davies
• Chemistry, Biochemistry and Cell Biology
• 42 min
  2. Peroxynitrite biochemistry oxidation and nitration reactions

  • Prof. Rafael Radi
• Oxidative Damage to Cellular Constituents
• 49 min
  3. Oxidatively generated damage to DNA: mechanistic aspects and formation in cells

  • Prof. Jean Cadet
• Cellular Protection Against Oxidative Stress
• 40 min
  4. Glutathione: antioxidant defense and regulation of its synthesis

  • Prof. Henry Jay Forman
• 34 min
  5. Vitamin E and the metabolic syndrome

  • Prof. Maret Traber
• Fertility, Growth, Development, Aging and Free Radicals
• 52 min
  6. Selenium and male fertility

  • Prof. Matilde Maiorino
• Free Radicals and Disease
• 54 min
  7. Oxidative stress and disease: atherosclerosis

  • Prof. Giuseppe Poli
• Archived Lectures *These may not cover the latest advances in the field
• 30 min
  8. The chemistry and biochemistry of partially reduced oxygen species

  • Dr. Willem Koppenol
• 44 min
  9. Chemistry and biochemistry of molecular probes used in the detection of reactive oxygen and nitrogen species

  • Prof. Balaraman Kalyanaraman
• 40 min
  10. Generation of reactive oxygen species by mitochondria

  • Dr. Enrique Cadenas
  • Dr. Derick Han
• 48 min
  11. Exercise and free radical generation by contracting skeletal muscle

  • Prof. Malcolm Jackson
• 42 min
  12. Lipid peroxidation: from basic mechanisms to clinical relevance

  • Prof. Jason Morrow
• 39 min
  13. Protein oxidation and removal of oxidized proteins by proteolysis

  • Prof. Tilman Grune
• 38 min
  14. Oxidative stress in aging

  • Dr. Jose Vina
• 43 min
  15. Oxidative stress in disease: cardiac ischemia/reperfusion injury

  • Prof. Jay Zweier
• 48 min
  16. How trypanosomes cope with oxidative stress

  • Prof. Leopold Flohe
• 58 min
  17. Oxidative stress in ALS

  • Prof. Dame Pamela Shaw
• 50 min
  18. Antioxidants and immune response and infectious diseases

  • Prof. Simin Meydani
• 39 min
  19. Oxidative stress in development and neonatal diseases

  • Dr. Phyllis Dennery
• 55 min
  20. Oxidative modification of brain proteins in Alzheimer's disease and models thereof: role of amyloid beta-peptide (1- 42) and insights from redox proteomics

  • Prof. D. Allan Butterfield
• 57 min
  21. Oxidative DNA damage: mechanisms, repair and disease

  • Prof. Miral Dizdaroglu
• 52 min
  22. Ubiquitin dependent degradation of proteins modified by oxidation, deamidation and glycation: role in vision

  • Prof. Allen Taylor
• 46 min
  23. Cell signaling by vitamin E

  • Prof. Angelo Azzi
• 20 min
  24. The SODs

  • Prof. Daret St. Clair

Printable Handouts

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Navigable Slide Index

1. Introduction
2. First description of ALS
3. Amyotrophic lateral sclerosis/MN disease
4. Plan of lecture
5. The normal human motor system
6. Normal vs. affected human spinal cord
7. Characteristics of affected motor neurons
8. TDP-43 protein in affected neurons
9. Motor neuron disease: clinical consequences
10. Spared motor neuron groups
11. Motor neuron disease prognosis
12. MNs: features underlying selective vulnerability
13. ALS/MND: a complex and multifactorial disease
14. Genetic factors in MND - Mendelian
15. Cu/Zn SOD1 product and its related gene
16. Cu/Zn SOD1 gene structure
17. SOD1 mutations
18. SOD1 mutations: loss of function?
19. SOD1 mutations: toxic gain of function
20. Potential mechanisms of neuronal oxidative stress
21. Causes of oxidative stress
22. Sources of intracellular oxidative stress
23. Mitochondria: energy generators of the cell
24. Mitochondrial free radical production
25. The mitochondrial electron transport chain
26. Intracellular reactive oxygen species (ROS)
27. Targets damaged by ROS
28. Anti-oxidant defence mechanisms
29. Mitochondrial anti-oxidant defence
30. Evidence for oxidative stress role in ALS/MND
31. NSC34 cell model
32. Use of NSC34 cell model
33. Mitochondrial morphology in NSC34 MN cells
34. Mitochondrial complex activity
35. Alteration in the mitochondrial proteome
36. Main altered proteins
37. Dichlorofluorescein assay
38. Oxidative stress measured by DCF in NSC34 cells
39. DCF assay validation
40. Protective effect of Ebselen on oxidative stress
41. Affymetrix GeneChips
42. Affymetrix system
43. Differential gene expression in MN cell line (1)
44. Differential gene expression in MN cell line (2)
45. Key transcriptome changes in MN cell line
46. Anti-oxidant related genes and pathways
47. The Nrf2-ARE signalling pathway
48. SOD1 G93A transgenic mouse model of ALS
49. Disease progression in mutant transgenic mice
50. Evidence for oxidative damage in transgenic mice
51. Oxidative stress in human ALS
52. CSF 3-nitrotyrosine levels
53. Isolating motor neurons from tissue sections
54. Peroxiredoxin 3 levels in human ALS
55. Causes of oxidative stress in ALS/MND
56. Major pathogenetic factors in ALS/MND
57. Consequences of SOD1 gain of function mutation
58. SOD1 chemistry
59. How does mutant SOD1 exert neurotoxic effect?
60. Glutamate-mediated injury to nerve cells
61. Glutamate-mediated injury of motor neurons
62. Normal glutamate neurotransmission
63. Excitotoxicity and ALS
64. Links between glutamate and oxidative stress
65. Oxidative stress and links with excitotoxicity
66. Mitochondria as targets for injury in ALS/MND
67. Mitochondrial dysfunction in motor neuron injury
68. Mitochondrial alterations in ALS/MND model cells
69. Mitochondrial dysfunction in mutant SOD1 mice
70. Evidence for mitochondrial dysfunction in humans
71. COX and SDH mitochondrial enzyme activities
72. Oxidative stress as a therapeutic target in ALS
73. Mechanisms of action of anti-oxidant drugs
74. Antioxidant treatment for ALS/MND
75. Clinical trials of anti-oxidant therapies in ALS
76. Ongoing trials of anti-oxidant therapies in ALS
77. Preclinical testing in SOD1 mutant mouse
78. Conclusions

Topics Covered

• Key facts
• The normal human motor system
• Motor neurone disease: clinical consequences
• Spared motor neurone groups
• Prognosis
• Features of motor neurones which may underlie selective vulnerability
• Complex and multifactorial disease
• Genetic factors
• SOD1 mutations
• Potential mechanisms of neuronal oxidative stress
• Sources of intracellular oxidative stress
• Mitochondrial free radical production
• ROS
• Evidence for the role of oxidative stress in ALS
• NSC34 cell model
• G93A mutant SOD1
• Oxidative stress in human ALS
• Major pathogenetic factors
• Glutamate
• Excitotoxicity
• Mitochondrial dysfunction
• Potential mechanisms of action of antioxidant drugs
• Clinical trials

Links

Series:

• Free Radicals and the Oxygen Paradox

Categories:

• Biochemistry
• Clinical Practice
• Neuroscience

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on November 1, 2007
• Archived on May 31, 2018

Financial Disclosures

• Prof. Dame Pamela Shaw has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.