Holly AllenCREUTZFELDT-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).

K u m a r a n , S u n i t h a P e t a l . “ D i ff u s i o n - W e i g h t e d I m a g i n g : A s t h e F i r s t D i a g n o s t i c C l u e t o C r e u t z f e l d t J a c o b D i s e a s e . ” J o u r n a l o f N e u r o s c i e n c e s i n R u r a l

P r a c t i c e 3 . 3 ( 2 0 1 2 ) : 4 0 8 – 4 1 0 . P M C . W e b . 2 3 F e b . 2 0 1 5 .

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

"Creu tz fe ld t - J akob D isease Fact Sheet . " : Na t iona l I ns t i tu te o f Neuro log ica l D i so rders and S t roke (N INDS) . Web . 4 Mar. 2015 . <ht tp : / /www.n inds .n ih .gov /d i so rders /c jd /deta i l _c jd .h tm>.

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 Saq ib Mahmood. “An Overv i ew o f Human Pr i on D i seases . ” Vi ro l ogy J ourna l 8 (2011 ) : 559 . PMC . Web . 4 Mar. 2015 .

CAUSE

253 amino acids protein

Exists in two forms: a normal cellular prion protein designated as PrPC and a pathogenic misfolded conformer designated as PrPSc.

The two forms diff er in secondary and tertiary structure but not in the amino acid sequence.

PrPSc is mostly beta sheets while PrP C is mainly alpha helices.

PrPSc oligomers catalyze the conversion of PrP C molecules into PrPSc fi brils, the breakage of which provides more PrP Sc templates for the conversion process.

I m r a n , M u h a m m a d , a n d S a q i b M a h m o o d . “A n O v e r v i e w o f H u m a n P r i o n D i s e a s e s . ” V i r o l o g y J o u r n a l 8 ( 2 0 1 1 ) :

5 5 9 . P M C . We b . 4 M a r. 2 0 1 5 .

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 , Ra lph e t a l . “NMR So lu t ion S t ructu re o f the Human Pr ion Pro te in . ” Proceed ings o f the Nat iona l Academy o f Sc iences o f the Un i ted S ta tes o f Amer ica 97 .1 (2000) : 145–150 .

Pr in t .

3-D STRUCTURE FOR PRPSC

the β-sheets fold into β-helicesKupfer, L, W Hinrichs, and M.H Groschup. “Prion Protein Misfolding.” Current Molecular Medicine 9.7

(2009): 826–835. PMC. Web. 16 Mar. 2015.

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 infl uence 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 fl uid, urine, and serum to try and determine the nature Creutzfeldt- Jakob disease.

"C re u t z f e l d t - J a ko b D i s e a s e Fa c t S h e e t . " : N a t i o n a l I n s t i t u t e o f N e u ro l o g i c a l D i s o rd e r s a n d S t r o k e ( N IN D S ) . We b . 4 M a r. 2 0 1 5 . < h t t p : / / w w w.n i n d s . n i h . g o v / d i s o rd e r s / c j d / d e t a i l _ c j d . h t m > .

RESEARCH