Reflection the 3rd: Creutzfeldt, Jakob, and I

Creutzfeldt-Jakob Disease (CJD) is the first documented and most common prion-based disease and in order to reflect the importance of this disease both as a significantly common enough terminal illness and as a rare prion disease should be reflected in the way it is represented. To accomplish this, there are three major themes that the information in the literature can be broken down into to help demonstrate the historical work that has led to our current understanding and the still very much important work that is going on now. These themes are cognitive degradation, spongification by amalyoids, and the prion protein itself.

The theme of cognitive degradation covers the clinical studies that were first to acknowledge, define, and segregate CJD as its own disease separate from other prion diseases. This initial body of information in the literature is important for historic reasons by documenting the progression of how we had come regard this disease as something fundamentally different from viral and bacterial diseases or even genetic disorders for that matter. This clinical information is also important to keep in mind when trying to understand the literature around the next two themes as all prion diseases are from a misfolding of the same protein which makes the same amalyoids and makes the same spongiform. The main difference between the diseases is the progression of cognitive function loss based on where the amyloid aggregates start forming first. Because the literature that falls within the next two themes isn’t yet complete, it is still relevant to keep this general clinical information in mind as we hypothesis more information and delve deeper into this disease.

The next theme to fit the literature’s information into of spongiform and amyloid aggregation isn’t as clear cut a grouping in terms of the type of research that would fall into this category as that of the clinical studies is to the previous theme. This theme has some historical overlap with the previous one as I’ve considered it to cover a range or literature that has done experimental research on CJD up until we get to work on the prion protein on its own. This means that this theme also holds some historic significant as it is the only form of experimental research that could really be done on this disease before the 1980’s, when genetic techniques in research started developing. This theme also incorporates the important work done to understand the formation and impact of the plaques of prion proteins that build-up and eventually solidify in the brain to cause it to spongiform.

The final theme for the information around the protein itself covers all literature that has research into structure, function, and specific interactions around the protease resistant conformation of the prion protein. This is the theme that contemporary literature is mainly focused on now and represents both the forefront and limitations of our understanding of prion diseases. It is also the least clinically specific theme out of the three as the work done on the prion protein could be based in the context of another prion disease but still have information relevant to CJD.

Like the number of themes, there are 3 major techniques or innovations that took place within the last 40 years of experimental based research moved the field forward and allowed for news understandings of CJD to be fleshed-out. This first is the idea and techniques necessary to take spongiform brains from victims of CJD and try to purify out a specific substance, namely the prion protein plaques. The second advance came along with the sequencing of DNA and proteins so that all of the identified protein amalyoid that had been previously researched can now be sequenced and the gene for the prion protein finally identified. The third major, and most recent advance, was the due to the increasing accessibility of transformation and genetic recombination such as in mice allowing for this disease to be artificially introduced and studied in a experimentally controlled environment.

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