Amyloid plaques

Question 1

Amyloid plaques consist of

Answer 1

Amyloid fibrils

Question 2

Amyloid fibrils consist of

Answer 2

“Cross beta structure” with beta strands perpendicular to the backbone structure

Question 3

APP

Answer 3

Amyloid precursor protein

Question 4

Typical behavior of a nucleation process

Answer 4

Long period followed by rapid build up

Question 5

Amyloidoses (examples)

Answer 5

Huntington disease, Alzheimer disease, Parkinsons etc

Question 6

Alzheimer’s disease (from what)

Answer 6

Abeta protein —> AAP (amyloid precursor proteins) —> plaques or amyloid fibrils (Same thing) (beta strands on long perpendicular fibers)

Question 7

Initiation of amyloid fibrillation

Answer 7

Seeded polymerization OR covalent modification of proteins (oxidation, phosphorylation, ubiquiton like modifier SUMOlaytion (small ubiquitin like modifier), proteolytic cleavage)

Question 8

How do these plaques lead to the death of the cells that harbor them?

Answer 8

prevailing hypothesis is that the BIG amyloid plaques aren’t the main problem, but the small aggregates of the same proteins cause intracellular damage

example: a plaque on mitochondria may cause the proton pump to be inhibited or stimulated, or leaky, causing apoptosis

Question 9

metals in proteins: what where how and important points

Answer 9

1) at least a quarter of proteins need metals
2) metallochaperonins deliver them
3) Certain heavy metals like Cd, Hg, and Pd are protein inhibitors

Question 10

Protein Viruses

Answer 10

transmissible aggregates

PrP (mad cow disease)—> PrP^sc
Amyloid plaques—> beta amyloid
alpha-synuclein—> plaques
SOD1 monomer —-> SOD1 plaques

Question 11

Amyloid fibrils (structure)

Answer 11

Core consists of enriched beta-sheets

fibrils are insoluble and form aggregates

the formation of aggregates are disease specific

they are transmissible