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Oxidative stress in amyotrophic lateral sclerosis (ALS) 2
Published on September 29, 2022 20 min
Other Talks in the Series: ALS and Other Motor Neuron Disorders
Cognition in ALS and the overlap with frontotemporal dementia (FTD)
- Dr. Thomas Bak
- University of Edinburgh, UK
What about other subtypes? What about other genetic causes and the 95% of patients that don't have a key autosomal dominant genetic change and have sporadic MND?
If you look in human tissue, again, you can find these biochemical footprints of free radical damage; nitrotyrosine residues, protein carbonyls, markers of lipid oxidation, markers of DNA damage. 8-hydroxy-2 deoxyguanosine is a key marker of oxidative damage to DNA. You can find that in brain and spinal cord tissue. You can also find similar biochemical changes indicating the presence of oxidative stress in the cerebrospinal fluid, the fluid that bathes the brain and spinal cord, and you can also find biochemical evidence of impaired antioxidant defence. Reduced expression of the peroxiredoxin enzyme, reduced expression of NRF2, and the downstream genes controlled by that transcription factor.
These are just some examples. These are indices of oxidative stress. This is 8-hydroxy deoxyguanosine. You can see it's elevated in ALS tissue compared to controls. This is isoprostane, again, elevated in MND patients compared to controls. Those oxidative stress biomarkers are there in patients with sporadic MND as well as those with SOD1 mutations.