Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is an adult-onset, progressive and fatal neurodegenerative disease. Pathologically, it is characterized by a loss of motor neurons in the spinal cord, brain stem and motor cortex leading to progressive muscle weakness, atrophy, and death. ALS presents as both a sporadic (SALS) and familial (FALS) illness. Interestingly, over 100 mutations of the CuZn-Superoxide Dismutase (SOD1) gene have been reported to be dominantly inherited in ALS families.
SOD1 is a 17KD protein that contains one copper and one zinc atom. The known function of this enzyme is to convert superoxide to oxygen and hydrogen peroxide. It was first thought that the toxicity of different SOD1 mutants linked to ALS resulted from decreased free-radical scavenging activity. However, studies show that mutant SOD1 enzymes cause motor neuron degeneration via a gain of harmful properties. The nature of the gain-of-toxic function in mutant SOD1 is not clear.
Recent studies suggest that SOD1 itself is a target of oxidative stress. Human SOD1 has four cysteine residues, Cys6, Cys57, Cys111, and Cys146. An internal disulfide bond exists between Cys57 and Cys146. This disulfide bond is highly conserved in SOD1, making the protein considerably strong, while the remaining two cysteine residues are free and prone to post-translational modifications.
Here we show that free cysteine residues in SOD1 are available to be modified by mal PEG (Maleimide polyethylene glycol) and AMS, and that this modification decreases with disease progression. Our data suggests that cysteine residues in SOD1 are post-translationally modified and may play a significant role in the development of the disease.
| Identifer | oai:union.ndltd.org:MANITOBA/oai:mspace.lib.umanitoba.ca:1993/4244 |
| Date | 23 September 2010 |
| Creators | Clayton, Leilanie |
| Contributors | Kong, Jiming (Human Anatomy and Cell Science), Vrontakis, Maria (Human Anatomy and Cell Science) Hombach-Klonisch, Sabine (Human Anatomy and Cell Science) Cheng, Keding (National Microbiology Lab) |
| Source Sets | University of Manitoba Canada |
| Language | en_US |
| Detected Language | English |
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