Lecture 34: Prions. PRION = Pr oteinaceous In fectious particle. Prion diseases can occur through:. Infection: Infectious As a dominantly inherited genetic disorder: Familial Consequent to a spontaneous mutation: Sporadic. Mammalian Prion diseases. .
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PRION = Proteinaceous Infectious particle
Prion diseases can occur through:
Characterized as Spongiform Encephalopathies.
Characterized by amyloid plaques or spongy (spongiform) appearance of the affected areas of the brain, due to accumulation of vesicular structures in the brains of infected organisms.
Vacuoles are seen in one neuron
and in the neuropiles. Astrocytes
with small nucleus proliferate. No
inflammatory cells infiltrae in the brain.
For many years, prion diseases were thought to be caused by slow-acting viruses, and were referred to as ‘slow virus diseases’, ‘transmissible spongiform encephalopathies’, or ‘unconventional viral diseases’.
Creutzfeldt-Jakob disease (CJD).
Characterized by a progressive dementia
Regional distribution of PrPSc in transgenic mice inoculated with brain extracts from humans who died of prion disease
Mouse inoculated with brain extract from FFI patient
Mouse inoculated with brain extract from fCJD (E200K) patient
Ventral posterior lateral thalamic nucleus
Mad Cow disease (Bovine Spongiform Encephalopathy or BSE)
Risks to human health
Other mammalian prion diseases
The Prion Protein (PrP).
Amyloid plaque stained with Congo Red
Bifefringence under polarized light
Prion protein gene structure.
However, PrP-null mice are fine. Therefore, PrP is not an essential protein.Molecular characterization of the PrP gene.
45,000X magnification electron micrograph of yeast prion protein
fibers formed in the test tube. The rigid fibers are similar to those
observed in amyloid diseases of mammals.
Propagation of the prion form of the proteins
Prion formation in vitro (yeast prion system)
Q: Does requirement for transmissability limit our conceptual understanding of prion disease?
By the allosteric model, any protein that can template a conformational change should also fit the definition.
Opens up new possibilities, e.g.
Altzheimers, Sickle Cell disease
Early-Onset Familial Alzheimer Disease With Coexisting-Amyloid and Prion Pathology (JAMA. 2000;283:1689-1691)
Figure. Double Immunostaining for -Amyloid and Prion Protein (PrP) in the Frontal Cortex
Senile plaques immunopositive for -amyloid40 (arrowheads in panels A and C), PrP106-126(arrowheads in B), and for -amyloid40 plus PrP106-126 (double arrowheads in C) are shown. Twodifferent chromogens were used, first diaminobenzidine dihydrochloride to reveal the -amyloid peptide (reddish-brown) and second, benzidine dihydrochloride to reveal the PrP106-126 (blue). When both signals are superposed, the blue signal appears dark and is localized in the center of the plaque.
Scale bar is 50 µm for panels A and B, and 75 µm for panel C.
transcription (missing from cellular RNAs?)
T.O. Diener (1987)
Potato spindle tuber viroid
chrysanthemum stunt viroid
Apple viroid disease
Avocado Sunblotch Viroid
Coconut cadang-cadang viroid
(HSVd) or narrow (CCCVd)
Developmental controls on movement as well
Moves from infected leaf to roots, up phloem to actively photosynthesizing leaves, then back down the plant
They’re genetically related to one another
HDV: hepatitis delta virus
Elena et al. 1991. Proc. Natl. Acad. Sci. USA 88, 5631-5634.