Holly Allen CREUTZFELDT-JAKOB DISEASE

 Human equivalent of mad cow disease  Rare, degenerative, fatal disease  Approximately 1 case per million per year  Typically people are diagnosed around age 60  CJD belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSEs). Kumaran, Sunitha P et al. “Diffusion-Weighted Imaging: As the First Diagnostic Clue to Creutzfeldt Jacob Disease.” Journal of Neurosciences in Rural Practice 3.3 (2012): 408–410. PMC. Web. 23 Feb WHAT IS CREUTZFELDT-JAKOB DISEASE?

 Rapidly progressive dementia  Problems with muscular coordination  Personality changes  Mental impairment becomes severe  Eventual loss of the ability to move or speak, which leads to coma which then leads to death "Creutzfeldt-Jakob Disease Fact Sheet." : National Institute of Neurological Disorders and Stroke (NINDS). Web. 4 Mar SYMPTOMS

 Creutzfeldt-Jakob Disease is caused by a type of protein called a prion.  Prion diseases are transmissible, progressive and fatal neurodegenerative conditions associated with misfolding and aggregation of a host-encoded cellular prion protein, PrP.  This type of disease can be hereditary but it can also occur sporadically.  Creutzfeldt-Jakob Disease is a sporadically occurring disease. Imran, Muhammad, and Saqib Mahmood. “An Overview of Human Prion Diseases.” Virology Journal 8 (2011): 559. PMC. Web. 4 Mar CAUSE

 253 amino acids protein  Exists in two forms: a normal cellular prion protein designated as PrP C and a pathogenic misfolded conformer designated as PrP Sc.  The two forms differ in secondary and tertiary structure but not in the amino acid sequence.  PrP Sc is mostly beta sheets while PrP C is mainly alpha helices.  PrP Sc oligomers catalyze the conversion of PrP C molecules into PrP Sc fibrils, the breakage of which provides more PrP Sc templates for the conversion process. Imran, Muhammad, and Saqib Mahmood. “An Overview of Human Prion Diseases.” Virology Journal 8 (2011): 559. PMC. Web. 4 Mar PRION PROTEIN (PRP)

 The normal Prion protein is harmless to the human body.  Once one misfolds they begin to clump together with other proteins and cause the properly folded proteins to misfold.  Prions do not contain genetic information and do not require genes to reproduce themselves, infectious prions can arise if a mutation occurs in the gene for the body’s normal prion protein. PRION PROTEIN

 The NMR structures of the human prion protein include a globular domain, two C-terminal fragments, and an N-terminal flexibly disordered “tail.”  The globular domain contains three α-helices and a short anti- parallel β-sheet.  Variations of local structure is related to the disease, CJD. NMR

 Zahn, Ralph et al. “NMR Solution Structure of the Human Prion Protein.” Proceedings of the National Academy of Sciences of the United States of America 97.1 (2000): 145–150. Print.

3-D STRUCTURE FOR PRP SC the β-sheets fold into β-helices Kupfer, L, W Hinrichs, and M.H Groschup. “Prion Protein Misfolding.” Current Molecular Medicine 9.7 (2009): 826– 835. PMC. Web. 16 Mar

 There is currently no treatment for CJD.  The symptoms can be alleviated but there is no cure, opiate drugs can help relieve pain if it occurs. TREATMENT

 Researchers are examining whether the transmissible agent is a prion or a product of an infection, and they are trying to discover factors that influence prion infectivity and how the disorder damages the brain.  Researchers are also trying to determe how abnormal prion proteins lead to disease  Scientists are conducting biochemical analyses of brain tissue, blood, spinal fluid, urine, and serum to try and determine the nature Creutzfeldt-Jakob disease. "Creutzfeldt-Jakob Disease Fact Sheet." : National Institute of Neurological Disorders and Stroke (NINDS). Web. 4 Mar RESEARCH