Format

Send to:

Choose Destination
See comment in PubMed Commons below
Prion. 2007 Jan-Mar;1(1):15-20. Epub 2007 Jan 6.

Protein misfolding and the serpinopathies.

Author information

  • 1Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom.

Abstract

The serpins are the largest superfamily of protease inhibitors. They are found in almost all branches of life including viruses, prokaryotes and eukaryotes. They inhibit their target protease by a unique mechanism that involves a large conformational transition and the translocation of the enzyme from the upper to the lower pole of the protein. This complex mechanism, and the involvement of serpins in important biological regulatory processes, makes them prone to mutation-related diseases. For example the polymerization of mutant alpha(1)-antitrypsin leads to the accumulation of ordered polymers within the endoplasmic reticulum of hepatocytes in association with cirrhosis. An identical process in the neuron specific serpin, neuroserpin, results in the accumulation of polymers in neurons and the dementia FENIB. In both cases there is a clear correlation between the molecular instability, the rate of polymer formation and the severity of disease. A similar process underlies the hepatic retention and plasma deficiency of antithrombin, C1 inhibitor, alpha(1)-antichymotrypsin and heparin co-factor II. The common mechanism of polymerization has allowed us to group these conditions together as a novel class of disease, the serpinopathies.

PMID:
19164889
[PubMed - indexed for MEDLINE]
PMCID:
PMC2633702
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Landes Bioscience Icon for PubMed Central
    Loading ...
    Write to the Help Desk