Protein Misfolding Diseases Flashcards Preview

Foundations Test 1 > Protein Misfolding Diseases > Flashcards

Flashcards in Protein Misfolding Diseases Deck (27)
Loading flashcards...
1

What things could cause misfolding?

Mutations, Post-translational mod, spontaneous processes

2

CF gene and what it codes for

CFTR for transport of chloride ions through membrane

3

Mutation of CF

Delta-F508 (phenylalanine) folding incorrectly and not transported to membrane
Phenylalanine is missing

4

Aggregation mechanism

Residues that like to associate are sufficiently exposed so that molecules have a reasonable probablility to sticking to one another

5

Amyloidoses caused by

Soluble proteins

6

Amyloidoses examples

Alz, Parks, Hunt, T2DM, prion, familial

7

Neurodegenrative amyloidoses vs. familial amyloidoses

Neuro - smaller deposits
Familial - larger

8

Transthyretin Amyloidosis...other name, inheritance, cause

Familial amyloid polyneuropathy
Autosomal dominant
Mutation (Val30Met) of transthyretin gene
Need liver transplant

9

Transthyretin structure

Homotetramer

10

All amyloid like deposits are

B-sheet rich

11

Remainder of protein besides B-sheet

Decorates outside of fibril
Other proteins stick as well

12

Huntington's Dz...inheritance, symptoms

Autosomal dom neurodegen disorder
Motor impairment, cog defects, personaliy changes

13

HD causes

Massive neuronal death and cell loss due to proteinaceous deposits in neural tissue

14

HD gene and mutation that occurs

Huntingtin
Has region with many glutamine-encoding codons (CAG) polyglutamine
In HD, glutamine codon is longer

15

Why does polyglutamine form amyloid-like structures?

Gln side chain can form H bonds with self like protein backbone
Have 2 layers

16

HD age of onset and cutoff

Longer polyglutamine sequence=earlier
32

17

AZ dz forms and what it is characterized by

Familial and sporadic (most common)
Plaques and tangles

18

Plaques from

Abeta

19

Tangles from

Tau

20

Abeta cleavage normal and in Az

Normal - alpha, gamma
Alz - beta, gamma
Forms longer peptide that can aggregate

21

Abeta formed by cleavage of

APP - amyloid precursor protein

22

Abeta peptide

Hydrophobic and can form hair-pin like structures
Abeta1-40 most common
Longer is worse (42)

23

Abeta peptides form what prior to fibril

Hairpin monomer, beta sheet oligomer, protofibril

Thought that smaller may be neurotoxic

24

Tau is

Microtubule binding protein

25

What happens to tau in alz

Hyperphosphorylated and aggregates...NOT driven by hydrophobicity

26

Other tauopathies

Frontotemporal dementia - no Abeta aggregates

27

Which comes first, A beta or tau

Abeta...could cause hyperphosphorylation by recruiting kinases...don't know