Analyzing the Identification of a Novel Biomarker for Parkinson’s Disease

Morgan McKeown ‘20,  Prof. William Church

5 thoughts on “Analyzing the Identification of a Novel Biomarker for Parkinson’s Disease

  1. Hi Morgan,

    I have a couple of questions:

    (1) Is the mobilization of UA, and the subsequent generation of products like triuert, specific to PD vs. other disorders?

    (2) It would appear from your scatterplot that triuret levels in (what I assume are) the PINK-1 KO mice are well within the normal range for WT animals until the animals reached the point of more than about 50% loss of SN dopamine. I’m also assuming these animals would also have symptoms of PD once 50% loss occurs. So how can this be useful for detecting PD earlier in the progression of the disease, if levels are normal up to the point of symptomology presenting?

    • Hi Professor Martinez,

      Thank you for your questions! As far as the first one, the breakdown of uric acid by reactive oxygen species like peroxynitrite, superoxide, or nitric oxide would produce the products triuret, allantoin, and 6-aminouracil in any pathogenesis, not just in Parkinson’s. This type of mechanism for oxidative damage producing triuret and the other products has actually been observed in a variety of conditions, one paper titled “Simultaneous determination of uric acid metabolites allantoin, 6-aminouracil,
      and triuret in human urine using liquid chromatography–mass spectrometry” by Kim, et. al, showed that the products (in urine, in this case) can be associated with oxidative damage as a result of smoking. I thought this paper was really interesting because it showed how this pathway of oxidative damage can be implicated in lots of different cases, I can definitely forward it to you if you’re interested! This also adds another layer to our research because it brings up the question of ambiguity of oxidative damage, and that is definitely something we would want to find a way to address in future studies.

      As far as your second question, I am a little confused. The y-axis of the scatterplot identifies concentrations of dopamine in the substantia nigra in ug/mL, not in percentages. However, it would definitely be helpful in a future study to include more data points at more ranging concentrations so that the correlation can be more directly seen. The hope is that we can begin to identify how decreasing concentrations of dopamine are correlated with increasing concentrations of triuret so that the serum of an individual could be analyzed and, if triuret concentrations are increased, we can begin to suspect that oxidative damage is occurring and that this damage is a result of Parkinson’s. It would also be helpful and interesting in the future to compare these levels to those from the serum of a WT animal, so that the differences between the two relationships can be more clearly seen.

      • Hi Morgan,

        Thank you for clarifying. I misunderstood the scatterplot Y-axis. You are absolutely on point with respect to the benefits of inclusion of WT animals in that data set that was plotted; it would give you a better understanding about whether there is good separation in the DA levels across groups and how that correlates to triuret level differences. But what is definitely needed here is a readout of symptom severity – if the goal is to have these kind of metabolite measure be a way to catch asymptomatic individuals before they experience significant dopamine depletion, as compared to the standard way of waiting until they are symptomatic to diagnose, it is essential to know if you can distinguish differences in triuret levels between WT animals and parkinsonian ones, before the parkinsonian ones are symptomatic. Otherwise, if the differences are only present in animals that are already symptomatic, the metabolite measure doesn’t provide any added benefit for the purpose of diagnosing prior to symptomology. Hopefully this makes sense.

        Best,

        Prof. Martinez

  2. Just realized that I said ug/mL for concentrations of dopamine in the scatterplot, and the concentrations are actually in ng/mL. My mistake!

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