Metabolism of amyloid proteins

Merrill Benson, B. Kluve-Beckerman, J. J. Liepnieks, J. R. Murrell, D. Hanes, T. Uemichi

Research output: Contribution to journalArticle

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Abstract

Metabolic processing of amyloid precursor proteins is an important factor in the genesis of practically all forms of amyloidosis. Of the three major forms of systemic amyloidosis, reactive amyloid (amyloid A protein; AA) formation shows the most consistent role of partial protcolysis of serum amyloid A (SAA) to AA proteins which form fibrils. Immunoglobulin amyloidosis is also usually associated with C-terminal degradation of the fibril precursor light chain protein. Although it is commonly thought that transthyretin amyloidosis is associated with fibril formation from the tetrameric circulating plasma transthyretin, chemical analyses of transthyretin fibril deposits show significant fragmentation of the fibril protein constituents. In addition, it has been documented that proteolytic fragments are the fibril subunit proteins in gelsolin, cystatin C, Alzheimer's β-amyloid precursor protein and apolipoprotein AI (apoAI) amyloidoses. Notable exceptions to the role of proteolysis in amyloid fibril formation would appear to be the lysozyme and β2-microglobulin amyloidoses. Few studies have examined the metabolism of amyloid-forming proteins. Perhaps the best data are on apoAI, which show decreased plasma residence time for the amyloidogenic Gly26Arg apoAI (1.8d vs. normal 4.5 d). Similarly, preliminary data show increased clearance of Va130Met transthyretin when compared with the wild-type protein (18 h vs. 26 h). Also, biosynthetically 35S-labelled SAA proteins reconstituted with HDL show increased plasma clearance of murine SAA2, the amyloid fibril subunit protein, when compared with murine SAA1. Few data are available on metabolism of amyloid immunoglobulin light chain proteins, but it has been shown that radiolabelled Bence-Jones proteins are cleared very rapidly from the circulation. A better understanding of the metabolism of precursor proteins in each of the amyloid deposition diseases will give insight into the mechanisms of fibril formation and pathogenesis of amyloidosis.

Original languageEnglish
Pages (from-to)104-118
Number of pages15
JournalCIBA Foundation Symposia
Issue number199
StatePublished - 1996

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Amyloidogenic Proteins
Amyloidosis
Serum Amyloid A Protein
Amyloid
Prealbumin
Amyloid beta-Protein Precursor
Apolipoprotein A-I
Protein Subunits
Proteins
Bence Jones Protein
Gelsolin
Immunoglobulin Light Chains
Cystatin C
Protein Precursors
Apolipoproteins
Muramidase
Proteolysis
Immunoglobulins
Light

ASJC Scopus subject areas

  • General

Cite this

Benson, M., Kluve-Beckerman, B., Liepnieks, J. J., Murrell, J. R., Hanes, D., & Uemichi, T. (1996). Metabolism of amyloid proteins. CIBA Foundation Symposia, (199), 104-118.

Metabolism of amyloid proteins. / Benson, Merrill; Kluve-Beckerman, B.; Liepnieks, J. J.; Murrell, J. R.; Hanes, D.; Uemichi, T.

In: CIBA Foundation Symposia, No. 199, 1996, p. 104-118.

Research output: Contribution to journalArticle

Benson, M, Kluve-Beckerman, B, Liepnieks, JJ, Murrell, JR, Hanes, D & Uemichi, T 1996, 'Metabolism of amyloid proteins', CIBA Foundation Symposia, no. 199, pp. 104-118.
Benson M, Kluve-Beckerman B, Liepnieks JJ, Murrell JR, Hanes D, Uemichi T. Metabolism of amyloid proteins. CIBA Foundation Symposia. 1996;(199):104-118.
Benson, Merrill ; Kluve-Beckerman, B. ; Liepnieks, J. J. ; Murrell, J. R. ; Hanes, D. ; Uemichi, T. / Metabolism of amyloid proteins. In: CIBA Foundation Symposia. 1996 ; No. 199. pp. 104-118.
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