Properties Of Amyloidogenic Proteins

To date, at least 21 different proteins have been recognized as causative agents of amyloid diseases.5 Despite heterogeneous structure and function, all these proteins generate morphologically indistinguishable amyloid fibrils. The current nomenclature for amyloidosis is based on this diversity of precursor proteins. For example, amyloidosis involving Ig light chains (L) or transthyretrin (TTR) is classified as AL or ATTR, respectively. The conversion of the native protein into a p-sheet structure is a pathologic process closely linked to physiologic protein folding. The pathogenically mis-folded proteins may form in several ways. The protein may have an intrinsic property to assume a pathologic conformation that becomes evident with ageing (e.g., normal transthyretin in patients with senile systemic amyloidosis),9 or with persistently high concentrations in the serum (e.g., p-2 microglobulin in patients undergoing long-term hemodialysis).10 Other mechanisms include mutations in the protein, as in many hereditary amyloidoses, or proteolytic remodeling of the precursors, as in p-amyloid precursors in Alzheimer's disease. The mechanisms can act independently or together. Other environmental influences, such as proteolysis, pH, and oxidation states, also seem to play important roles in the formation of amyloid fibrils.11

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