Prion Diseases

Question 1

What percentage of human prion diseases are inheritable?

Answer 1

15%

Question 2

what percentage of human prion diseases are sporadic?

Answer 2

85%

Question 3

How many cases of rare prion diseases occur each year?

Answer 3

1-2 million.

Question 4

Prion is the abbreviation of a full term. What is the full term?

Answer 4

Proteinaceous infectious particle

Question 5

What does a proteinaceous infectious particle mean?

Answer 5

This is a misfolded protein segment that is transmissible and induces disease in healthy people.

Question 6

How are the prion proteins made?

Answer 6

The prion form is simply a misfolded version of a normal healthy protein found in all humans. So, when the prion form is transmitted into the healthy person, the prion’s instruct the healthy proteins to misfold aswell, so that all the healthy proteins in the normal person become prions also.

Question 7

What is scrapie and how does it work?

Answer 7

The scrapie prion is called the PrPsc (Sc for scrapie). The PrPc is the normal version of this protein found sheep. The PrPsc then orders the conversion of healthy PrPc into PrPsc. The accumulation of PrPsc causes the disease scrapie.

Question 8

What is the protein-only hypothesis?

Answer 8

This hypothesis states that the prion form of a protein is the only factor that causes the healthy form of the protein in a healthy host to become misfolded and infectious.

Question 9

Describe the PrPc Protein.

Answer 9

The PrPc protein is the healthy basic form of protein found in sheep. It is a protease sensitive, soluble protein with an alpha-helix structure. It is abundant in many tissues.

Question 10

Describe the PrPsc protein.

Answer 10

The PrPsc protein is the infectious, misfolded version of the PrPc protein. It is protease resistant, and so once in the body it cannot be destroyed. It is an insoluble protein with a beta-sheet structure.

Question 11

What are the two major pieces of evidence that point to PrPsc as a prion?

Answer 11

1. PrPsc levels are proportional to the extent of disease.

2. It is the major protein that is co-purified with PrPc in prion infected tissue.

Question 12

What gene transcribes the PrPc and PrPsc proteins?

Answer 12

The PRPN gene does. This gene encodes the healthy PrPc version, which is later mutated to form the PrPsc version.

Question 13

What is the relationship between the PrPsc and the amount of PRNP gene?

Answer 13

The more PRPN gene copies one has, the more severe the prion infection.

Question 14

PrPc is found not only in the brain, but in most body tissue. If PrPsc is injected into non-membrane bound PrPc, does it still induce pathology?

Answer 14

No. This is because PrPsc only induces prion diseases in the brain’s PrPc called Membrane anchored PrPc. Non membrane anchored PRPc cannot be misfolded.

Question 15

What is the evidence to prove the protein-only hypothesis. Basically, that all you need is PrPc and PrPsc together, to produce more PrPsc.

Answer 15

1. Studies have been conducted where PrPc and PrPsc were combined in a bottle, outside of the body. They discovered that time was the only factor, and that the more time the two spent together in the bottle, the more PrPc misfolded.

Question 16

So, if all it takes to produce PrPsc is to misfold, PrPc, then if you misfolded PrPc in a lab without PrPsc, then could you still produce PrPsc?

Answer 16

No. Instead, you would produce a 3rd type of PrP protein called PrPres. PrPres is another misfolded form of PrPc. It behaves differently to PrPsc because it is not transmitable and does not induce prion disease. PrPres contributes to amyloid deposition in the brain and neurological disease.

Question 17

Are there different strains of PrPsc, or is there only one strain?

Answer 17

PrPsc has 2 strains in hamsters. The hyper-strain with a short incubation period which affects the brainstem and cerebellar cortex. Then there is the drowsy-strain, which affects the hippocampus and needs long incubation periods.

Question 18

Are there human strains of PrPsc? If so, how can we tell the difference?

Answer 18

There are human strains. If PrPsc is allowed to be digested by protein kinase in a lab, then seperated by electrophoresis, you will see seperated strains based on how far they have moved on the electrograph. If there was only one strain, there should be only one solid mass on the graph.

Question 19

Are other proteins in the body able to be misfolded into prions aswell?

Answer 19

The evidence suggests that most proteins can also become prions, but not many of them are easy to transmit when misfolded.

Question 20

When the PrPsc accumulates in the brain, can it induce pathology in other parts of the body?

Answer 20

Yes. So far, the GI tract is the other place where the PrPsc attacks. This causes the weight loss and loss of GI tract functioning evident in prion disease sufferers.

Question 21

What triggers sporadic prion disease? Or in other words what causes a healthy body with only healthy PrPc, to start to misfold and produce PrPsc?

Answer 21

Events that change the charge of glycosaminoglycans could trigger prion disease.