11

Question 1

What is the process for protein folding (4)

Answer 1

1) Unfolded, newly synthesised polypeptide
2) Folding intermediates - Chain collapse: hydrophobic force favours burial of non-polar residues
3) Stable, folded globular protein: formation of native interactions and stable globular structure

Question 2

Which diseases are caused by improper trafficking (2)

Answer 2

Cystic fibrosis

Familial hypercholesterolemia

Question 3

What diseases are the result of a toxic conformer (3)

Answer 3

Alzheimer's disease
Transthyretin amyloidosis
Mad cow disease
Type II diabetes
Cataracts

Question 4

What diseases are the result of protein degradation (3)

Answer 4

Scurvy
Gaucher’s disease
Cystic fibrosis

Question 5

What results from defective collagen synthesis (3)

Answer 5

Wound healing
Fragile connective tissue
Bleeding

Question 6

How does hydroxy-pro work

Answer 6

Provide thermal stability to collagen triple helix
Requires prolyl hydroxylase
Fe2+ essential

Question 7

What occurs during protein misfolding diseases

Answer 7

Deposition of fibrillar aggregates

Question 8

What does electron microscopy and X-ray fibre diffraction studies show with amyloidoses

Answer 8

Common morphology and core, repeated B-sheet scaffold structure

Question 9

What are common features of amyloid fibrils

Answer 9

1) Long, straight and unbranching
2) Give cross-B x-ray diffraction pattern
3) All stain in diagnostic way

Question 10

Which stain fluoresces when bound to amyloid

Answer 10

Thioflavin T

Question 11

Which stain shows green birefringence when bound to amyloid

Answer 11

Congo red

Question 12

What does cross-b pattern in x-rays suggest

Answer 12

All amyloid fibrils have same underlying regular repeated structure, extended B-sheet

Question 13

What are some causes of incorrect protein folding (4)

Answer 13

1) Elevated protein levels
2) Mutations
3) Abnormal chaperone response
4) Aging

Question 14

What are two hallmarks of Alzheimer’s disease

Answer 14

1) Extracellular amyloid plaques composed of Ab peptide surrounding neurons
2) Neurofibrillary tangles within neurons

Question 15

How is beta amyloid protein processed from Alzheimer’s precursor protein (APP)

Answer 15

B-secretase

Y-secretase

Question 16

What are some therapeutic strategies against amyloid (3)

Answer 16

1) Small molecules to prevent Ab production
2) Vaccines/antibodies against soluble Ab
3) Antibodies to reduce plaque aggregate burden

Question 17

What are some AD treatments targeting Ab (5)

Answer 17

1) Vaccine AN1792
2) Anti-Ab monoclonal antibodies
3) Glycosaminoglycan mimetic
4) PBT2 prana zinc chelator
5) Y-secretase and B-secretase inhibitors

Question 18

What forms amyloid plaques in Parkinson’s Disease

Answer 18

A-synuclein

Question 19

What is early-onset PD associated with

Answer 19

Mutations in a-synuclein

Question 20

What do mutant forms of a-syn that give rise to early-onset familial PD do

Answer 20

Assemble into small oligomers faster than WT