02a: Protein Folding Diseases

Question 1

Diseases of protein folding are formally called:

Answer 1

Proteopathies

Question 2

Neurodegenerative diseases typically due to:

Answer 2

Protein aggregation (accumulation of misfolded protein)

Question 3

Protein aggregation, leading to disease, happens (inside/outside) neurons.

Answer 3

Either!

Question 4

Do prions have DNA or RNA?

Answer 4

Neither

Question 5

Prions are what type of molecules?

Answer 5

Naked protein molecules

Question 6

How are prion diseases acquired?

Answer 6

1. Infection
2. Genetically inherited
3. Sporadically

Question 7

Prion diseases develop (slower/quicker/same as) compared to other neuro degenerative diseases.

Answer 7

Quicker

Question 8

Scrapie is a (X) disease found in:

Answer 8

X = prion

Sheep

Question 9

BSE or (X) disease is a (Y) disease found in:

Answer 9

X = bovine spongiform encephalopathy (Mad Cow)

Y = prion

Cows

Question 10

CWD or (X) disease is a (Y) disease found in:

Answer 10

X = chronic wasting

Y = prion

Deer and elk

Question 11

CJD or (X) disease is a (Y) disease found in:

Answer 11

X = Creutzfeldt-Jakob Disease

Y = prion

Humans

Question 12

Kuru disease is a (Y) disease found in:

Answer 12

Y = prion

Humans

Question 13

Which clinical features are found in prion diseases, but not other neuro degenerative diseases like AD?

Answer 13

Muscle symptoms (ataxia, tremors, myoclonus)

Question 14

T/F: prion diseases, unlike AD, don’t cause dementia.

Answer 14

False

Question 15

Describe neuropathology of prion diseases.

Answer 15

1. Spongiform change in brain

2. Amyloid plaques

Question 16

Kuru has similar pathology to which other prion disease?

Answer 16

Scrapie

Question 17

Which prion diseases are familial (inherited)?

Answer 17

CJD, GSS, FFI

Question 18

Were the first BSE cases inherited, infectious, or sporadic?

Answer 18

Infectious (from sheep scrapie) or sporadic

Question 19

How were the first cases of CJD acquired?

Answer 19

Infection by eating contaminated beef

Question 20

What’s a PrPc? Function?

Answer 20

Normal cell-surface protein (unknown function)

Question 21

Is PrPc infectious?

Answer 21

No

Question 22

T/F: PrPc is monomeric.

Answer 22

True

Question 23

T/F: PrPsc is monomeric.

Answer 23

False - aggregated

Question 24

What’s the composition of secondary structure in PrPc?

Answer 24

3% beta sheets

40% alpha helices

Question 25

What’s the composition of secondary structure in PrPsc?

Answer 25

40% beta sheets

30% alpha helices

Question 26

T/F: PrPsc is protease-resistant.

Answer 26

True

Question 27

What differs in AA sequence between PrPc and PrPsc?

Answer 27

No difference in AA sequence (only in conformations/folding)

Question 28

Do prions transfer info via mechanism that’s similar to bacteria or viruses?

Answer 28

Neither; propagate protein conformation, but no inheritance of nucleic acid sequences

Question 29

Prion disease propagates in (specific/unspecific) manner.

Answer 29

Highly specific

Question 30

(X) people are affected by AD. How will this change by 2050?

Answer 30

X = 5 million

Will triple

Question 31

Describe the neuropathology of AD.

Answer 31

1. Neurofibrillary tangles (intracellular)

2. Neurotic plaques (extra cellular)

Question 32

What’s the peptide associated with neurotic plaques?

Answer 32

A-beta

Question 33

What’s the peptide associated with neurofibrillary tangles?

Answer 33

P-tau (MT-associated protein)

Question 34

Secretase (stimulators/inhibitors) are treatment for AD.

Answer 34

Inhibitors

Question 35

New trials for AD therapy are targeting which patients?

Answer 35

Pre-symptomatic (ex: PS1 mutation patients)

Question 36

What are some important biomarkers of AD found in (blood/urine/CSF/other)?

Answer 36

Blood and CSF

A-beta and P-tau

Question 37

What’s florbetapir?

Answer 37

New A-beta amyloid tracer