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Prion Disease Transmission

Short overview of the background of the paper:

The study is focused on researching and the reasons, which cause a number of neurological diseases and, therefore, come closer to the solution, which would allow modern medicine to more effectively cope with this problem. The study is dedicated to prionoses, which are, in general term, the diseases characterized by neurodegeneration, in its turn caused by the fact that cellular prion protein (PrPC) is misfolded; accumulation of its elements in the brain and PrP amyloid deposits can be addressed as possible indication at the presence of the disease. Molecular Chaperones (MCs) are causing the response of unfolded protein. However, their role is in pathogenesis of researched neurological diseases, on which the work is focused.

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Key results analysis:

The study describes the response of MCs registered with laboratory mice, which have been previously infected with scrapie strains. Basically, two types of response were registered. The responses showed the difference between ME7 and 87V strains and 22L and 139A respectfully. In the first case, amyloid deposition is inducted while in the latter, such deposits have not been found. The response type, which is similar to the first pattern, was also registered with the mice of APPPS1-21 Alzheimer's transgenic type. One of the main ideas, at which the results of the study indicate, that there may be different mechanisms of regulating MCs may be present, and they depend on the presence of amyloidogenic or non-amyloidogenic prion strains. The results of the study also showed that amyloidogenic and non-amyloidogenic prion strains cause MCs to respond in a different way. This may be a very significant factor, contributing to the phenotypical differences, which ave been registered among prion strains.

The authors of the study underline that the experiments, which involved animals, were held in strict accordance to the provisions of “guide for the care of laboratory animals” developed by the National Institute of Health. Institutional Animal Care and Use Committee also approved the experiments. The authors also state that everything possible was done in order to bring the suffering of the animals to the minimum and to use as few animals as it was possible.

Upregulation of Grp58 (its selective type) was registered associated with 22L and 139A strains, and Grp78 and Grp94 were subject to selective upregulation in the case with the mice, infected with ME7 and 87V. It was also ascertained that hereditary prionoses in their cellular form become the reason for retention of misfolded PRP and its further proteasomal degradation (Jin et al., 2000).

Modern studies indicate at the fact that misfolding of PRP within models of cellular type associated both with hereditary and infectious prionoses cause “ ER Ca2+ homeostasis and sensitize cells to endoplasmic reticulum stress”(Torres et al., 2010).

Summary of significance:

In general, it is clear from the article that the team of researchers conducted a very important and thorough study of the problem. They also held experiments, which are of extreme importance for the humans and have been carried out in a way, which made sure that animals were not mistreated. Thus, unnecessary sufferings were not caused to the experimental animals.

The article, definitely, includes a very clear and strong abstract and goals, which importance is clearly explained in the beginning of the article. The arguments supporting the authors’ viewpoint are quite logical and rest on solid scientific data and literature analysis (27 sources are being cited within the article), and reasonable experimental data is also being analyzed and given clear interpretation. The paper, however, is not written in a simple language, and presupposes serious and deep knowledge of the subject discussed; therefore, additional research was required to understand some of the article’s parts. The selection of the works cited in the article and the theoretical provisions cited by the authors are in correspondence with the article’s topic.

The conclusions of the article are supported by the results of the experiments and with theoretical base, which is being analyzed for the article. The explanations of results are accurate and precise; however, they may appear to be not clear enough for somebody who is not very well familiar with the subject. Nevertheless, more detailed and simplified explanations might have been presented to the increase the article’s size, which is absolutely unnecessary, since the article is being addressed to the readers familiar with the subject and work in the same direction as the authors of the publication. Unfortunately, the article lacks clear conclusions, and the points discussed are not summarized in the end of the article.

It is possible to conclude that the overall organization of the article is quite reasonable. The argumentation is strong and is based on accurate data and thorough literature analysis. However, one of the drawbacks of the article is the absence of a clearly articulated conclusion, which would sum up all the information provided in the article. Nevertheless, this circumstance does not substantially detract from its importance and the significance of the findings discussed in it since the article is of great scientific value and contains very important and valuable information and analysis.

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