Download Creutzfeldt-Jakob Disease - Clayton State University

CREUTZFELDT-JAKOB
DISEASE
Holly Allen
WHAT IS 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. 2015.
SYMPTOMS
 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. 2015. <http://www.ninds.nih.gov/disorders/cjd/detail_cjd.htm>.
CAUSE
 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. 2015.
PRION PROTEIN (PRP)
 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. 2015.
PRION PROTEIN
 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.
NMR
 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 antiparallel β-sheet.
 Variations of local structure is related to the disease, CJD.

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. 2015.
TREATMENT
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.
RESEARCH
 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. 2015. <http://www.ninds.nih.gov/disorders/cjd/detail_cjd.htm>.