Creutzfeld-Jakob Disease

Karan Saravana

Patient Zero’s Symptoms

Patient Zero starts exhibiting symptoms of dementia. Bipolar-like symptoms start to appear followed by anxiety, depression, paranoia, and other psychological symptoms.

Physical symptoms soon appear, such as speech impairments, myoclonus, ataxia, and seizures.

Neurological function deteriorates

CJD DiagnosisThese specific symptoms suggest CJD

CJD is a neurodegenerative disease that comes from the scrapie infection. The scrapie infection is famous for also causing mad cow disease.

CJD causes destruction of brain tissue which creates a holy appearance like swiss cheese.

This disease is fatal and does not have a cure as of yet.

PrionsCJD is caused by Prions: misfolded proteins that transform normal proteins into prions.

The prions cause large quantities of insoluble proteins that leads to plaque buildup.

Plaque causes the neurons in the brain to be “blocked” creating a barrier to proper neurological function.

Prions (cont.)Normal proteins exist in their a-helix form

Infectious Prion proteins, however, are misfolded into a b-sheet form.The b-sheet prions can attract more a-helix proteins into becoming more b-sheet proteins. The b-sheet proteins adhere to each other to create amyloid plaque. (also found in Alzheimeric neurons)

Prion Biochemistry

A-helix rich “cellular” prion (PrPC) is converted to a pathogenic, fibril forming, isoform PrPSC (scrappie). This prion is characterized by its insolubility, its high B-sheet content and its protease resistance. This is a two step mechanism:

The patient is exposed to a nucleated PrPSC protein. The nucleation of the infectious prions cause them to appear as “seeds” or in a crystalized form. The crystals already contain B-sheets.

The seeds adhere to the PrPC to create a heterodimer. In this complex, the a-helixes of the PrPC fold into B-sheets in a process that is not completely understood by modern science.

Prion Biochemistry

(cont.)The reformed B-sheets of the prior PrPC half of the heterodimer then becomes identical to the PrPSC half forming a homodimer.

The homodimer then attracts more homodimers creating large macromolecules of amyloid plaque.

The plaque then fragments into several more “seeds” furthering the process converting more PrPC into the infectious PrPSC

TreatmentCurrently no treatment exists for CJD. However, there is one potential solution.

Scientists are suggesting the use of proteins interference to inhibit the spread of the infectious prions.

Protein interference works (theoretically) by inhibiting gene expression in the PrPSC proteins. This would be accomplished by adding specific Dicer proteins that specifically adhere to the seeded prion. The Dicer would cleave the B-sheeted prion into small fragments which would dissipate into the cytoplasms.

Theoretically, this would eliminate the possibility of amyloid build up in the brain.

Works Cited"Biochemistry and Structure of PrPC and PrPSc." Biochemistry and Structure of PrPC and PrPSc. N.p., n.d. Web. 16 Dec. 2016.

Gu, Yaping. "Pathogenic Mutations in the Glycosylphosphatidylinositol Signal Peptide of PrP Modulate Its Topology in Neuroblastoma Cells." Molecular and Cellular Neurosciences. U.S. National Library of Medicine, Apr. 2008. Web. 16 Dec. 2016.

"The Role of GPI-anchored PrPCin Mediating the Neurotoxic Effect of Scrapie Prions in Neurons." Current Issues in Molecular Biology (2010): n. pag. Web.