Biochemical basis of Amyloidosis and Prion disease

3. Write the biochemical basis of,  

a) Amyloidosis

 Natural protein (amyloid precursor) has a membrane spanning domain 
 In this disease abnormal proteolytic cleavage of membrane spanning domain occurs
 This fragments remain in the extracellular compartment and they cannot complete the natural folding process
 They form aggregates of β pleated sheets (amyloids)
 β Pleated sheets are secondary structures 
 These fibrillar deposits are toxic to the tissues eg: brain
 And cause degenerative diseases (Alzheimer’s disease) 

b) Prion disease 

 Natural non-infectious form of prion protein is found in human brain cells, they have alpha helical structure
 Infectious particles have beta pleated structure
 Thus infected beta pleated sheet act as a template & converts naturally occurring alpha helical structure to beta pleated sheets  These fibrillar beta pleated sheets form insoluble aggregates of fibrils
Eg; mad cow disease     
Bovine spongiform encephalopathy     
Creutzfeldt Jacob disease/ kuru in humans     
Scrapie in sheep