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Ip, Philbert et al. “Quercitrin and quercetin 3-β-d-glucoside as chemical chaperones for the A4V SOD1 ALS-causing mutant.” Protein engineering, design & selection : PEDS vol. 30,6 (2017): 431-440. https://doi.org/10.1093/protein/gzx025
ALS, otherwise known as amyotrophic lateral sclerosis, is a disorder that affects the brain and spinal cord by wkilling motor neurons that allow the body to move. Some symptoms of ALS include progressive paralysis, where the body slowly begins to lose the ability to move, and death. Research has shown that around 1% of all ALS cases are caused by a mutation in the DNA of the SOD1 gene that produces an enzyme that can break down superoxide radicals. These superoxide radicals contribute to the production of reactive oxygen species(ROS), chemicals that can kill cells and damage DNA. Although SOD1 is responsible for only 1% of cases, if researchers are able to fully understand the mechanism behind SOD1, this can help them understand the other 99% of unknown cases as that specific mechanism will likely affect a specific pathway that other cases also impact. Thus, the researchers in this study decided to identify specific compounds that would prevent the build-up of ROS and would also help prevent SOD1 from mutating.
The experimenters ran a series of procedures using computers where they were able to test hundreds of potential treatment molecules in a simulation to see how they would fare when their receptors interact with mutated SOD1. From this procedure they discovered that 7 molecules stood out: EGCG, quercitrin, quercetin 3-β-d-glucoside, nicergoline, benzopurpurine 4B, chenodeoxycholic acid, and huperzine A. The researchers then tested these 7 chemicals on mutated SOD1 extracted from cells to see if they would be able to prevent further variation from developing in the gene, which could lead to ALS.
They discovered that both quercitrin and quercetin 3-β-d-glucoside showed that they were capable of preventing further variation, attributing this ability to their inherent roots as part of the plant Astragalus membranaceus, which is commonly used in Chinese herbal medicine. Both compounds originate from Astragalus membranaceus, which has been proven to decrease ROS via its antioxidant properties that can prevent damage to organic molecules and can prevent the prognosis of ALS. This evidence led the researchers to believe that this quality is what allowed for quercitrin and quercetin 3-β-d-glucoside to inhibit the aggregation of the mutated SOD1.
In order to test this theory the researchers conducted another experiment where they utilized other compounds with antioxidant properties to test if they would also be able to prevent mutated SOD1. However, the results showed that these other compounds were ineffective, meaning that both quercitrin and quercetin 3-β-d-glucoside have an unknown quality that allows them to impede further formation of mutated SOD1. The researchers plan on further exploring this mechanism in their future trials and testing for any potential negative effects.
Summarised by Brenton Lee
Works Cited
Lai, Patrick Kwok-Kin et al. “Isolation of anti-inflammatory fractions and compounds from the root of Astragalus membranaceus.” Phytotherapy research : PTR vol. 27,4 (2013): 581-7. doi:10.1002/ptr.4759
Li, Ai-Ping et al. “Exploration the active compounds of Astragali Radix in treatment of adriamycin nephropathy by network pharmacology combined with transcriptomic approach.” Journal of ethnopharmacology vol. 258 (2020): 112537. doi:10.1016/j.jep.2019.112537
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