Prions are infectious protein particles that cause neurodegenerative diseases like Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy (mad cow disease) in cattle. Prions are composed solely of protein and contain no nucleic acids. They propagate by converting the normal cellular prion protein (PrPC) into an abnormal disease-causing form (PrPSc). The normal prion protein is involved in the replication of the mutated form. Prion diseases are difficult to treat as prions are highly resistant to heat and chemical inactivation.

1. Prions
 Proteinaceous infectious particle
 an infectious agent made only of protein, containing no
nucleic acids
 The PRNP gene encodes for the prion protein (PrP)
 PrP is active in the brain and several other tissues
 The normal form of the protein is called PrPC, while the
infectious form is called PrpSc

2.  Prions are toxic because they are not denatured easily and can
accumulate in the body.
 Prions can be ingested via taunted meat and maybe transported by the
immune system to the brain where they cause damage. (scientists still
are not certain who they get transported)
 Moral of the story feeding cows animal by-products to save money is
not safe for humans.

3. Proposed mechanism of prion propagation

4. Prion replication
Note that normal PrPC is involved in replication of mutated PrPSc

5. Molecular model of PrPc and PrPSc structures Protein
refolds abnormally
 Normal prions contain about 200-250 amino acids twisted into three
telephone chord-like coils known as helices, with tails of more amino
acids.
 The mutated, and infectious, form is built from the same amino acids
but take a different shape.
 100 times smaller than the smallest known virus.
Normal Disease Normal Disease

6. Prion vs Bactera & Viruses
 Prions do not contain nucleic acid; they don’t have DNA
or RNA.
 They are extremely resistant to heat and chemicals.
 Prions are very difficult to decompose biologically; they
survive in soil for many years.

7. Prion Diseases
 Humans:
CJD (Creutzfeldt Jakob Disease)
GSS (Gerstmann Straussler Syndrome)
 Cattle:
BSE (Bovine Spongiform Encephalopathy, better known as Mad
Cow Disease)
 Sheep:
Scrapie
 Deer/Elk:
CDW (Chronic Wasting Disease)

8. Symptoms of prion disease in humans
 Rapidly developing dementia
 Difficulty walking and changes in gait
 Hallucinations
 Muscle stiffness
 Confusion
 Fatigue
 Difficulty speaking

9. Prions Access the Brain
 It is believed that the immune system plays a big role in
neuroinvasion.
 Follicular Dendritic Cells (FDCs) being that they are mobile
could function as the bridge between the GI tract and the
lymphoid organs, where the prions can replicate.
 The process by which prions are transported is not fully
understood, further research is needed.

10. Normal Mutated
Kuru and vCJD are known to be transmitted to humans who have eaten
the meat or brains of infected animals or, in the case of Kuru, infected
humans.

12. Creutzfeldt-Jakob Disease (CJD)
 Occurs worldwide
 Annual incidence (U.S.): ~1 case per million population
 Median age at death (U.S.): 68 years
Clinical features:
 Patients usually present with dementia, visual problems, or
cerebellar dysfunction
 Subsequent neurologic signs include myoclonus, tremors, and
rigidity
 Neurologic signs deteriorate very rapidly  akinetic mutism

13. Forms of CJD
 CJD occurs in three different forms:
 sporadic
 familial
 iatrogenic

14. Sporadic CJD
 About 85% of CJD patients
 No recognizable mode of transmission identified
 May be caused by:
Age-related somatic mutation of the prion protein gene
Error in production of the normal prion protein

15. Familial CJD
 About 10-15% of CJD patients
 Autosomal dominant inheritance
 Associated with prion protein gene abnormalities
 Usually a family history of CJD is present

16. Iatrogenic CJD
 1% of CJD patients
 Transmission through:
 Human Growth Hormone
 Dura Mater Graft
Lyodura
 Cornea transplantation
 Use of neurosurgical instruments and EEG depth electrodes

17. Prion disease diagnosis
 MRI scans of the brain
 Samples of fluid from the spinal cord (spinal tap)
 Electroencephalogram, which analyzes brain waves; this painless
test requires placing electrodes on the scalp
 Blood tests
 Neurologic and visual examinations to evaluate for nerve damage
and vision loss

18. Bovine spongiform encephalopathy
(BSE) or mad cow disease
 This is a fatal neurodegenerative disease of cattle
 An epidemic in British cattle occurred when farmers started to
use animal by-product as the main source of feed for their cattle.
 This lead to an over all higher rate of infection and disease.
 Mad cow disease is an incurable, fatal brain disease that affects
cattle and possibly some other animals, such as goats and sheep
 The causative agent for Mad Cow disease are prions
Prion is short for “proteinaceous infectious particle.”

19. Severe symptoms of BSE disease on humans
 Sudden nervousness or aggression. A person may develop destructive
behavior or actins while they are still live.
 Abnormal posture, which means that you may stand up or sit in a an
abnormal way, and not even realize it.
 Difficulty walking, which does not allow people to get up and will stay
paralyzed until a long time.
 Severe muscle twitching. This means that the muscles suddenly start to
move sharply or on an abnormal way.
 Rapid weight loss
 Lack of a good appetite- The disease can cause you not to eat anything
anymore

20. Classic Creutzfeldt-Jakob disease vs. Creutzfeldt-
Jakob disease (vCJD)
Characteristic Classic CJD Variant CJD
Median age of death 68 years 28 years
Median duration of illness 4-5 months 13-14 months
Clinical signs and symptoms Dementia; early neurological
signs
Prominent
psychiatric/behavioral
symptoms; painful
dysesthesias; delayed
neurological signs