Protein Misfolding and Disease Flashcards Preview

Molecules to Cells > Protein Misfolding and Disease > Flashcards

Flashcards in Protein Misfolding and Disease Deck (23):
1

What percentage of synthesized polypeptide chains are misfolded during or after synthesis?

As many as 50%

2

What factors contribute to increased protein misfolding?

Over-production
Impaired degradation
Mutations
Heat Shock
Absence of binding partners
Alterations in post-translational processing
Oxidative stress
Aging

3

What are the two possible outcomes of a misfolded protein?

Gain of function: toxicity
Loss of function: loss of biological function

4

What are amyloid fibrils?

Accumulations of misfolded proteins into beta sheets (perpendicular beta strands to the fiber axis)

Dyed with congo red or thioflavin

5

What disease is characterized by amyloid plaques?

Alzheimers

6

Are amyloids always pathogenic?

Nope

7

How are misfolded proteins dealt with in the cytoplasm?

JUNQ (degradation -> eventually goes to proteasome)

OR

IPOD (aggregation)

8

What determines whether misfolded proteins go to JUNQ or IPOD?

Ubiquitination status...

Ubiquitinated proteins go to JUNQ for degradation

IPOD proteins just get sequestered away and sit there

9

What are some major diseases of protein misfolding?

Alzheimer's
Huntingtons
Parkinsons
ALS
Tauopathy

10

What plaques form in Alzheimer's

Extracellular amyloid plaques/Abeta plaques which is made from amyloid precursor protein (APP)

Neurofibrillary tangles (Tau)

11

What protein deposits form in Parkinson's

Lewy bodies outside neurons

12

Do prion proteins have DNA or RNA?

NO!

13

What is characteristic of CJD?

Spongiform encephalopathy/vacuolation of the grey matter of the brain

14

What are human prion diseases?

Creutzfeldt-Jakob Disease (CJD)
Kuru
Gerstmann0Straussler Syndrome (GSS)
Fetal Familial Insomnia (FFI)

15

What are clinical features of prion diseases?

Dementia
Ataxia
Tremor
Myoclonus (involuntary muscle jerks)

16

What is the incubation period of prion diseases?

Years

17

What are infectious prion diseases?

Kuru, BSE, vCJD, CWD

18

What are genetic prion diseases?

CJD, GSS, FFI

100% penetrance

19

Can CJD also be sporadic?

Yes

20

What are the two forms of prions? How are they the same/different?

PrPC = non-infectious

PrPSc = infectious

Same AA sequence but different folding!

21

Describe PrPc

Normal cell-surface protein
Non-infectious
Monomeric
ALPHA HELIX

22

Describe PrPSc

Infectious
Diseases
Aggregated
BETA SHEET

23

What percentage of Alzheimer's cases are inherited?

10% 3 known genes