Amyloidosis Flashcards Preview

Y elective pathobiochemistry > Amyloidosis > Flashcards

Flashcards in Amyloidosis Deck (15)

Diseases involving amyloid proteins.

Creutzfeldt Jakob disease

Bovine Spongiform Enceophalopaty,
in humans causes variant CJD.

Kuru, transmitted from brain cannibalism




Gerstmann Ataxia

Fatal Familial Insomnia


Levinthals paradox

It would take longer time than the universe has existed for a protein of significant length to fall into its most thermodynamically stable state by random trial and error.

Chaperones are therefore a required/universal part of protein folding, it is a cooperative process with folding occurring actively in segments as the protein is transcribed


What are the functions of chaperones

1) To aid in the correct folding

2) to prevent formation of aggregates and amyloid fibrils.


What are some human chaperone proteins

HSP40, HSP70, HSP 90


What are the proteins responsible for protein ubiquitinylation

E1 E2 E3

E1 enzyme along with ATP binds to the ubiquitin protein.
The E1 enzyme then passes the ubiquitin protein to a second protein, called Ubiquitin carrier or conjugation protein (E2).
The E2 protein complexes with an Ubiquitin protein ligase (E3).

E3 ubiquitinylates the target.


What are the proteins responsible for targeting proteins to autolysosomes?


p61, ubiquitin binding protein p62, sequestosome

NBR1, Autophagy cargo receptor protein


What tertiary structure change is characteristic for amyloids

Proteins that contain many alpha helices in their properly folded form,

Convert to parallel beta-pleated sheets.

Overlap one another and form long amyloid fibrils


Why are they called amyloid deposits?

They stain similarly to starch - aka amylose - so researchers called them all amyloid before they knew they were proteins.


What special stain is unique for amyloid

Congo red

They show red-green birefringence under visible-polarized light respectively


Types of amyloidosis (systemic)

AL, AA, Abeta, TTR, Beta2-microglobulin

AL: Amyloid light chain, from Ig light chain protein

AA: Amyloid associated. From Serum Amyloid A protein. SAA acute phase protein.

Abeta amyloid: from amyloid beta protein found in alzheimer's disease. Generated by cleavage from the synaptic membrane protein APP, amyloid precursor protein.
In extracellular plaques in the brain and also deposited in CNS vessels.

ATTR: Transthyretin.
Serum TRANSport protein for THYRoxine and RETINol.
Mutated TTR proteins cause familial amyloidosis with polyneuorpathies, and cardiac deposits

Beta-2 microglobulin: Component of the MHC class 1 protein. A normal serum protein that causes amyloidosis in long term dialysis patients. It is not removed by dialysis and accumulates.


Cause and symptoms of primary amyloidosis

It is the AL class

Caused by hypersecretory clone of plasma cells causing Ig Light chain secretion

Bence Jones proteins in blood and urine.
Microinfarcts and obstruction of the kidney tubules. Eventual renal failure.

Macroglossia, gigantic tongue


Cause and symptoms of secondary amyloidosis

AA class
Caused by chronic inflammatory disorders, constant low grade liver APR activation, chronic SAA secretion.

Affects the kidney again

Also causes Rheumatoid arthritis due to immune complex deposition.


ATTR cause and symptoms

Point mutation causing transthyretin amyloid formation.

Familial disease

Or seen in elderly as senile ATTR.

Causes polyneuropathy
Restrictive cardiomyopathy from deposits.
Diastolic failure of the ventricles, and dilation of the atria.


Types of localized amyloidosis

Skin, lichens.


What gene/protein mutations are is causative for both Fatal Familial Insomnia and Gerschmann Ataxia?

PrP protein, Major Prion Protein

From the PRNP gene. PRioN Protein.

The PrP protein in its prion form is also the causative infectious agent in Creutzfeld Jakob disease, Kuru, and BSE