02a: Protein Folding Diseases Flashcards
Diseases of protein folding are formally called:
Proteopathies
Neurodegenerative diseases typically due to:
Protein aggregation (accumulation of misfolded protein)
Protein aggregation, leading to disease, happens (inside/outside) neurons.
Either!
Do prions have DNA or RNA?
Neither
Prions are what type of molecules?
Naked protein molecules
How are prion diseases acquired?
- Infection
- Genetically inherited
- Sporadically
Prion diseases develop (slower/quicker/same as) compared to other neuro degenerative diseases.
Quicker
Scrapie is a (X) disease found in:
X = prion
Sheep
BSE or (X) disease is a (Y) disease found in:
X = bovine spongiform encephalopathy (Mad Cow)
Y = prion
Cows
CWD or (X) disease is a (Y) disease found in:
X = chronic wasting
Y = prion
Deer and elk
CJD or (X) disease is a (Y) disease found in:
X = Creutzfeldt-Jakob Disease
Y = prion
Humans
Kuru disease is a (Y) disease found in:
Y = prion
Humans
Which clinical features are found in prion diseases, but not other neuro degenerative diseases like AD?
Muscle symptoms (ataxia, tremors, myoclonus)
T/F: prion diseases, unlike AD, don’t cause dementia.
False
Describe neuropathology of prion diseases.
- Spongiform change in brain
2. Amyloid plaques
Kuru has similar pathology to which other prion disease?
Scrapie
Which prion diseases are familial (inherited)?
CJD, GSS, FFI
Were the first BSE cases inherited, infectious, or sporadic?
Infectious (from sheep scrapie) or sporadic
How were the first cases of CJD acquired?
Infection by eating contaminated beef
What’s a PrPc? Function?
Normal cell-surface protein (unknown function)
Is PrPc infectious?
No
T/F: PrPc is monomeric.
True
T/F: PrPsc is monomeric.
False - aggregated
What’s the composition of secondary structure in PrPc?
3% beta sheets
40% alpha helices
What’s the composition of secondary structure in PrPsc?
40% beta sheets
30% alpha helices
T/F: PrPsc is protease-resistant.
True
What differs in AA sequence between PrPc and PrPsc?
No difference in AA sequence (only in conformations/folding)
Do prions transfer info via mechanism that’s similar to bacteria or viruses?
Neither; propagate protein conformation, but no inheritance of nucleic acid sequences
Prion disease propagates in (specific/unspecific) manner.
Highly specific
(X) people are affected by AD. How will this change by 2050?
X = 5 million
Will triple
Describe the neuropathology of AD.
- Neurofibrillary tangles (intracellular)
2. Neurotic plaques (extra cellular)
What’s the peptide associated with neurotic plaques?
A-beta
What’s the peptide associated with neurofibrillary tangles?
P-tau (MT-associated protein)
Secretase (stimulators/inhibitors) are treatment for AD.
Inhibitors
New trials for AD therapy are targeting which patients?
Pre-symptomatic (ex: PS1 mutation patients)
What are some important biomarkers of AD found in (blood/urine/CSF/other)?
Blood and CSF
A-beta and P-tau
What’s florbetapir?
New A-beta amyloid tracer
