Flashcards
prion disease 1
Cards in this deck (37)
- 1Origin of Kuru disease1920s
fore people of Highland region of Papa New Guinea - 2incubation period of Kuru disease4-50 years
patient overcome by the disease typically after 1-2 years after the onset of the symptoms - 3why was research into the cause of the Kuru disease not considered to be of important to western medicine20 000 people (particularly children and women) died because of Kuru
-
only affected a small number of people in a remote area. - 4what are the symptoms of Kuru- Neurological disorder causeing the patients to lose muscle control
- Starts with joint pain and after a short period infected patients will fall over and are unable to control muscle movement or stand unassisted- wasting away and unable to each - 5notable difference between Kuru and other neurological diseasesThey do not suffer from dementia- as other neurological diseases
- 6what can be said of the prevalence of Kuru in the 1960s- In the 1960s the prevalence of the disease decreased significantly--> in the mid 50s Australia took over papa new guinea and an example of colonialism having a positive effect
- The reason that the disease was seen to be far less prevalent was because the Australians ordered the tribes to stop their transmutation mourning ritual (cannibalism- after death as a way of showing love and respect) - 7why were women and children mainly affected by Kuru- Women of the village cooked and prepared the meal of the villager and this was given to the closest relative of the deceased- this was almost exclusively by women
- The brain was eaten - 8what did the scientist link Kuru with after the cause of the disease was discoveredScrapie
- 9what is believed to be the source of KuruThrough epidemiology it has been possible to trace the source of the disease to a single individual and it is likely that this person suffered sporadic CJD, and this spread through transumption
- 10describe the experiments of Daniel Gajdusek- Nobel prize winner 1976Repeated the animal experiments
- Take samples from child that had died of Kuru- removing a portion of the brain
- This sample was injected into chimps
- Expected the experiment would take 10 years- after 2 years the chimps began to suffer from clear Kuru like symptoms and analysis of the brain of the chimps showed the same histology
- Brain of a person that dies from Kuru appears to be destroyed and sponge-like --> these diseases are called spongiform diseases - 11what is CJDCreutzfeldt-Jakob Disease
- 12describe the symptoms of Creutzfeldt-Jakob Disease- I in every couple million people were affected
- Similar symptoms to Kuru- except that dementia is one of the key and early signs
- Ataxia- inability to stand, sit caused by loss of muscular control was the same
- Brain from a patient was taken and injected to a chimp - the same results as the Kuru brain were seen
- Closely related diseases - 13what did Gajdusek believe the source of CJD wasbelieved the cause of the disease was a slow virus- he was wrong
- 14name human prion diseases (transmissible spongiform encephalopathy)Kuru
Creutzfeldt-Jakob Disease
Gerstmann- Staussler syndrome
fatal familial insomnia
variant Creutzfeldt-Jakob Disease - 15name animal forms of transmissible spongiform encephalopathy (prion diseases)Scrapie
transmissible mink encephalopathy
chronic wasting disease of Elk
Bovine spongiform encephalopathy
feline spongiform encephalopathy - 16when was the last case of Kurulast case died in 2005
- 17when was there an emergence of vCJD80/early 90s
- 18what does the prion mis-folding disease causethe mis-folding of the prion protein
- 19what is chronic wasting disease- Norway had to kill herds of wild reindeer suffering from the prion disease; chronic wasting disease
- 20what are the 3 ways that prion disease can occurthe most common occurance of the disease is sporadic such as CJD- 1/2 in a million cases that sporadically develop CJD (not involving mutations- can be caused by somatic mutations but not clear)
- 15% of prion diseases are caused by mutations in the gene that encodes prion protein (PRNP gene) - these are the Gerstmann- Staussler syndrome and fatal familial insomnia
latrogenic and dietary - 21mutation of what gene causes contraction of a prion diseasePRNP gene
-15% of cases - 22how can infection of prion disease occurlatrogenic and dietary
Iatrogenic - contaminated growth hormone--> taken from human cadavers (if these have been taken from human cadavers that are infected with CJD are known to have transmitted the disease, grafts and instruments
Dietary- Kuru, vCJD and BSE - 23what causes different prion diseasesprion diseases have distinct clinical presentation and symptoms despite the underlying cause of the disease being the same (misfolded prion protein)
- 24what is the BSE crisis- Mid 80s epidemic affecting 100 thousands of cattle that presented symptoms that were similar to Scrapie
- Crisis for British agriculture and a medical crisis - 25what was the cause of the BSE crisis- Cattle fed on animal meal produced from the carcasses of sheep and other cows because this was protein rich and was though to help the cattle build muscle quickly
Rendering process of the carcasses for the animal feed involved procedure of autoclaving under pressure (<130c), change in procedure where the temperature was lowered to 121c and the time was reduced - 26why did changing the preparation of animal feed cause BSEThis change resulted in BSE -the prion is an extremely stable particle that can withstand these conditions (more likely to have emerged sporadically than through the contraction from scrappie from a sheep (although this is a possibility- it is thought to be less likely)
- 27what does BSE stand forBovine spongiform encephalopathy
mad cow disease - 28what was the economic effect of the BSE crisis- Export ban on british beef--> hitting agriculture
- Only country where this has broken out --> economical impact
- Not able to grow certain breeds of cow many regulations put on the cattle industry - 29medical implication of the BSE outbreakIrrespective of the origin of BSE, BSE prions are very likely to be the cause of many prion diseases emerging in the 1980s including vCJD (same prion strain)
- 30how many people died as a consequence of vCJD after the BSE crisis and why may this not be the final number178 people
--> however it is entirely possible that there is more deaths that will occur as a consequence of this epidemic --> Kuru = incubation period can be extremely long --> up to 50 years - 31How was it proven that the vCJD was as a consequence of the consumption of beef?- Consumption timing and geographical distribution of the vCJD strongly suggestive of a direct connection with BSE crisis
- Possible that the prions that are consumed as food are infectious and can cause disease - 32other than ingestion, how can prion diseases be contracted from outside sources (not mutation)Contraction of prion diseases through aerosols
It may also be possible to contract prion diseases through aerosols
- Inhaling aerosol of prions
- Shown in mice
- Sprayed with an aerosol that contained the prions
- Didn’t test if the prions can leave a patient in this way- infection can be taken up in different routes and is potent - 33describe the work of Stanley prisonerreceived Nobel prize in 1997 for his work on the prion protein
Coined the name prion- proteinaceous infectious particle that lacks nucleic acid - 34what is the definition of the prionsPrions are lethal mammalian pathogens composed of aggregated conformational isomers of a host encoded glycoprotein and which lack nucleic acids
- 35what was shown through the work of Stanley PrusinorPrusiner isolated the infectious agent of these diseases
Realised he had isolated protein- no DNA or RNA (not a virus or an infectious agent as we knew at the time)
Met by incredible resistance- especially by Gajdusek who was sure of his theory of a slow virus - 36stanley Prusiner suggested the prion hypothesis, what is this?prion disease are causes by amyloidogenic proteins
- The infectious prion form ((PrPsc)scrapie form of the protein) has a different structural confirmation than the normal protein ((PrPc)this is the cellular form) and is able to propagate this change among other molecules of the same protein
- Misfolded form of the protein imprints its structure and infection onto the cellular protein --> propagation within molecules of the same kind by merely contacting it - 37what is the prion problem? - the further questions that remain unansweredIt needed to be established what the structure of the PrPsc and PrPc were?
is there is species barrier?
What is the molecular basis of the prion strains resulting in distinct disease phenotypes--> as with virsues there seems to be strains that cause there to be different symptom?
What is the cause of the neurodegeneration?
What is the physiological function of the PrPc?
- Not possible to rule out that this is a loss of function disease as the function is not known-- however, we can predict that this probably a disease that is due to a gain in toxicity.
Information
- Description
- Protein structure and function Flashcards on prion disease 1 , created by Samantha bruce on 06/12/2019.
- Created by
- Samantha bruce
- Views
- 1
- Rating