What is the role of proteolysis in the pathogenesis of amyloidosis?

Updated: Nov 12, 2018
  • Author: Robert O Holmes, Jr, DO; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Answer

In some types of amyloidosis (eg, always in AA, often in AL and ATTR), the amyloid precursors undergo proteolysis, which may enhance folding into an amyloidogenic structural intermediate. In addition, some of the amyloidoses may have a normal proteolytic process that is disturbed, yielding a high concentration of an amyloidogenic intermediate. For example, it was shown that the mast cells of allergic responses may also participate in the development of secondary or amyloid AA in chronic inflammatory conditions. Mast cells hasten the partial degradation of the SAA protein that can produce highly amyloidogenic N-terminal fragments of SAA. However, factors that lead to different organ tropisms for the different amyloidoses are still largely unknown.

Whether the proteolysis occurs before or after tissue deposition is unclear in patients in whom beta protein fragments are observed in tissue deposits. In some types of amyloid (eg, AL, Aβ, ATTR), nonfibrillar forms of the same molecules can accumulate before fibril formation; thus, nonfibrillar deposits, in some cases, may represent intermediate deposition.


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