Prion Diseases Flashcards
What are Prions
Proteinaceous Infectious particles
Prion = native protein with infectious & pathogenic misfolded state
- No nucleic acid
- Characterised by neurodegenerative disease in all species
- No evidence of conventional host immune response
- subviral in size
transmissible spongiform encephalopathies (TSEs)
- Caused by Prions
-group of rare, fatal neurodegenerative diseases that affect humans and animals
-scrapie (sheep)
-BSE (cows)
-Creutzfeldt-Jakob Disease CJD & kuru (humans)
Treatment
- No screening test or treatment at present
- Clinical assesment
- Check for prion gene mutations
- Brain biopsy
- Brain examination at autospy
Prion Portien
Encoded by host gene Prnp
PrPc = native (cellular) form found in neurons of healthy animals. role?
PrPSc = pathogenic form - same sequence, different folding
Pathogenicity in Prion Disease
- Abnormal form of prion protein (prPSc) acts in a self-sustaining manner in the body (spreads) causing progressive and ultimately fatal prion disease
- Self-Replication: induces misfoling to abnormal conformation leading to exponential amplification of abnormal prions in the brain
- Protease resistance - Resistance of enzymes to break down proteins Encoded by host gene Prnp
-Heat resistance (autoclaving insufficient) - Insolubulity
- Aggregation - form fibrils
- Infectious nature: Ingestion, transplantation, expsosure to contaminated tissues
- Lack of immune response: often go unrecognised by immune system- evade clearance mechanisms
3 forms of Creutzfeldt-Jakob Disease (CJD) in human
Sporadic CJD; most common form, occurs spontaneously without known cause
Genetic (familial) CJD: caused by inherited mutations in the PRNP gene. polymorphism at codon 129 Met/Val -susceptibility to sporadic CJD
Accquired (infectious) CJD: very rare, occurs through exposure to infected brain/nervous tissue typically through medical procedures such as transplants, contaminated surgical instruments or certain hormone treatments.
3 pathogenic mechanisms for prion diseases
Infectious prion disease - Pathogenic prion protein transmitted between animals or humans
Sporadic prion disease - Random misfolding of normal prion protein in uninfected individual
(1 in a million)
Inherited prion disease- Mutation in Prnp yields a protein that changes more often into pathogenic form
What is Kuru Disease
1950s/60s epidemic
1100 deaths
rare and fatal neurodegenerative disorder that was once prevalent among the Fore people of Papua New Guinea.
caused by prions, infectious proteins that trigger abnormal folding of normal cellular proteins in the brain
- transmitted through ritualistic cannibalism
Examples of accquired CJD?// infectious diseases caused by prions
Kuru
Iatrogenic CJD eg human growth hormone, neurosurgery, corneal transplant
Variant CJD (vCJD)
Kuru disease symptoms
Unsteady gait, tremors lead to loss of ability to walk and then to sit up, slurring of speech, incontinence, difficulty swallowing
Prognosis: Death within three months to two years of the first symptoms,
Control of kuru disease
decline of cannibalistic practices among the Fore people
implementation of public health measures to discourage such practices
Bovine Spongiform Encephalopathy (BSE) (aka mad cow disease)
- Prion disease in cattle emerging in UK in 1996
- When humans consume meat products contaminated with BSE prions -> risk of developing variant CJD (vCJD)
How did BSE spread amongst cattle
- primarily through the practice of
feeding rendered meat and bone meal (MBM) from infected cattle to other cattle. Lack of Surveillance and Regulation.
: to prevent its spread (public health measures). Spread Within Herds
Control measures/ social / financial implications of BSE
- link between BSE and vCJD in humans was finally accepted
- control measures for cattle:
Banned the removal of brains, eyes and spinal cords in slaughterhouses. EC banned export of beef, beef banned on school dinners.
- Massive scandal happened even though the BSE cattle outbreak was on the decline.
- although the risks were gone from been the damage had been done: cull of 4.5 million cattle, £1.4 billion in compensation to farmers, £0.5 B on carcass disposal.
- 177 total cases tracked by Jhon gummer 17 years later showing no cases seen in anyone born after 1990
vCJD: people affected were young (28 was the median death age)
What caused BSE/vCJD?
Meat & bone meal (MBM), Recycling infected animal material into feed, Contaminated beef products into many products for human use, Poor tracking & record keeping, Poor slaughterhouse conditions, Long asymptomatic incubation period & lack of diagnostic screen
