AAT Bioquest

Dopamine-Mediated Oxidation of Methionine 127 in α-Synuclein

Despite all the advances made in medicine over the past century, there are some conditions for which researchers are still struggling to find a cure. However, this is not because not enough attention has been paid to searching for therapies, but rather because some of these conditions are so complex that researchers still do not have a full understanding of how they come about and how they should be subsequently treated. One clear example of this is Parkinson's disease (PD). A neurodegenerative disorder, Parkinson's is believed to be brought on by the selective degeneration of dopamine (DA) neurons and the formation of α-synuclein (α-syn)-containing Lewy bodies in the substantia nigra, with the subsequent loss of their terminals in the striatum. Much of the research to date points to a link between dopamine and α-syn, but it is not fully understood why PD pathogenesis occurs in some dopaminergic neurons and not in others. As a result, it is important to further study this relationship to be able to fully understand the pathology of PD, which is essential if an effective treatment is to be found in the near future.

This was the primary focus of a study conducted by Nakaso et al. from the Tottori University Faculty of Medicine in Japan. In their study, they took a closer look at the biological mechanisms taking place when DA and α-syn interact. Since Hydrogen Peroxide (H2O2) is known to be a clear indicator of oxidative stress, measuring levels of this substance was critical to determining the exact workings of this process. To do this, researchers used the Amplite Fluorimetric Hydrogen Peroxide Assay Kit, known to produce robust, accurate, and reliable readings of H2O2 levels, as well as to reveal intriguing cellular pathways related to oxidative stress. In doing so, they were able to closely monitor what was happening on a cellular level and see what missing links were present in the understanding of the relationship between DA and α-syn.

What they found should prove to be a large step forward for research into the causes and potential cures of PD. Nakaso and his team found that α-syn targets DA where there is a strong presence of M127, and that it is the main target of oxidative degradation induced by dopamine. Additionally, they found substances Y125 and S129 to act as enhancers of this modification. This is significant because it helps to resolve the question of selectivity. Researchers now have a clearer idea as to which cells stand to be affected by the interaction of DA and α-syn, and this increased understanding of the biological mechanisms behind PD will help make the search for a cure that much more directed. Results like this depend on the quality of the readings obtained during the study. By using the Amplite Fluorimetric Hydrogen Peroxide Assay Kit, the research team was assuring itself that the measurements they took of H2O2 were accurately reporting oxidative stress. This allows for researches to report results with high levels of reliability, and this helps confidently push the research community closer to finding safe and effective treatments for serious conditions such as Parkinson's disease.



  1. Nakaso, Kazuhiro, et al. "Dopamine-mediated oxidation of methionine 127 in α-synuclein causes cytotoxicity and oligomerization of α-synuclein." PLoS One 8.2 (2013): e55068.

Original created on July 31, 2017, last updated on July 31, 2017
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