NR AJFM
AU Parmar,J.S.; Lomas,D.A.
TI Alpha-1-antitrypsin deficiency, the serpinopathies and conformational disease
QU Journal of the Royal College of Physicians of London 2000 May-Jun; 34(3): 295-300
PT journal article
AB Alpha-1-antitrypsin deficiency results from point mutations that distort the structure of the protein to allow a unique protein-protein interaction that we have termed loopsheet polymerisation. Polymers of Z alpha 1-antitrypsin accumulate within hepatocytes to form inclusion bodies that are associated with juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein predisposes the Z alpha 1-antitrypsin homozygote to emphysema. This process also occurs in other members of the serine proteinase inhibitor (serpin) superfamily, antithrombin, C1-inhibitor and alpha 1-antichymotrypsin, in association with thrombosis, angioedema and chronic obstructive pulmonary disease, respectively, and we have recently shown that it underlies a novel inclusion body dementia. The interaction provides a useful paradigm for other 'conformational diseases' such as Huntington's disease, Creutzfeldt-Jakob disease and the amyloidoses.
MH Amyloidosis/*physiopathology; Creutzfeldt-Jakob Syndrome/*physiopathology; Human; Huntington Disease/*physiopathology; Inclusion Bodies; Polymers; Protein Conformation; Serpins/*pharmacology; alpha 1-Antitrypsin/*chemistry; alpha 1-Antitrypsin Deficiency/*complications/physiopathology
AD Cambridge Institute for Medical Research. jsp35@hermes.cam.ac.uk
SP englisch
PO England