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The putative role of alpha‐1‐antitrypsin in the disaggregation of amyloid lambda fibrils
Author(s) -
ERIKSSON S.,
JANCIAUSKIENE S.,
MERLINI G.
Publication year - 1995
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.1995.tb01154.x
Subject(s) - medicine , amyloid fibril , fibril , lambda , amyloid (mycology) , alpha (finance) , computational biology , biophysics , pathology , disease , amyloid β , biology , surgery , physics , construct validity , optics , patient satisfaction
. Background and objectives . Interactions between hydrophobic compounds like cholesterol and lithocholic acid and alpha‐1‐antitrypsin (α‐1‐AT) have previously been described. We studied the putative interaction between α‐1‐AT and the insoluble, hydrophobic, β‐pleated sheet, light‐chain‐derived fibrils that predominate the tissue deposits in primary immunocytic (AL) related amyloidosis. Subjects and methods . Amyloid fibrils were isolated from two cases with lambda and two cases with kappa AL amyloidosis. Results . The lambda fibrils could be completely disaggregated (as shown by light and electron microscopy and Congo red uptake) by α‐1‐AT added in the molar ratio 1:5, whereas fibrils with predominantly kappa chains remained unaffected. The lambda‐chain interaction was accompanied by characteristic changes of the physicochemical and biological properties of α‐1‐AT apparent in an increased thermal stability and loss of elastase‐inhibitory activity. These findings are compatible with a transition of α‐1‐AT from a native, stressed conformation to a relaxed form. Conclusions . Disaggregation of lambda AL amyloid fibrils can be achieved by addition of α‐1‐AT. The findings may have therapeutic implications in primary amyloidosis.