Handout 9 - Prions

More documents

Recommendations

Info

3/26/2006 5. Crucial experiment: •Mice carrying a murine transgene with the 102P-L GSS mutation spontaneously develop a lethal scrapie like disease. Brains also contain infectious prions because transmission to recipient animals has been demonstrated. Mice lacking the PrPc gene develop normally, no evident physiological or behavioural problems. Suggests that loss of PrPc function is unlikely to be the cause of disease rather accumulation of PrPsc is responsible. 3/26/2006 5. Crucial experiment: When inoculated with prions they do not develop disease. There are obvious implications here for the livestock and pharmaceutical industries and treatment of familial cases. Animals expressing reduced levels of PrPc are also resistant to infection - perhaps more immediately relevant to human disease. Animals overexpressing PrPc are more likely to develop prion diseases.
3/26/2006 Evidence against the prion model: •The existence of many different strains of scrapie (at least 15: latency, lesion patterns differ) which can be propagated in the same inbred mouse strain. These can transmit serially without changes in properties in the same mouse strain homozygous for a single PrP genotype. Cannot argue that there a distinct PrPc is converted to distinct PrPsc. Must mean that a common PrPc is corrupted in a different way, seems improbable but there is now experimental support for it. So how can a protein be infectious? A likely possibility is that the difference between PrPc and PrPsc is conformational. It is proposed therefore that this protein can adopt two quite different stable conformations. The safe PrPc form is normally adopted but rarely it can switch to the PrPsc form. Mutations favour this switch. It is proposed that PrPsc is transdominant and converts PrPc to PrPsc in an exponential fashion. 3/26/2006
Page 1 and 2: 3/26/2006 3/26/2006 PRIONS Definiti
Page 3 and 4: Humans diseases • The modified fo
Page 5 and 6: 3/26/2006 Replication In normal cel
Page 7 and 8: Pathologies induced by prions The p
Page 9 and 10: Pathologies induced by prions These
Page 11 and 12: 3/26/2006 Prion Diseases Prion dise
Page 13 and 14: Humans are also susceptible to seve
Page 15 and 16: Humans might be infected by prions
Page 17 and 18: 2. PrPsc is associated with scrapie
Page 19: 4. Mutated gene can cause susceptib
Page 23 and 24: Treatment •PrPc overexpression fa

Handout 9 - Prions

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?