Polymerisation underlies alpha1-antitrypsin deficiency, dementia and other serpinopathies.

alpha1-Antitrypsin deficiency, chronic obstructive pulmonary disease and the serpinopathies.

alpha1-Antitrypsin is the prototypical member of the serine proteinase inhibitor or serpin superfamily of proteins. The family includes alpha1-antichymotrypsin, C1 inhibitor, antithrombin and neuroserpin, which are all linked by a common molecular structure and the same suicidal mechanism for inhibiting their target enzymes. Point mutations result in an aberrant conformational transition and th...

Isoelectric Focusing and PCR-RFLP Joined Techniques for Alpha1-antitrypsin Deficiency Detection

53 persons suspected to alpha1-antitrypsin deficiency detection (AATD) were investigated for ZZ, MZ, ZS, SS, and MS alleles analysis by serum protein electrophoresis (SPE), measurement of trypsin inhibiting capacity (TIC), isoelectric focusing (IEF), polymerase chain reaction (PCR), and IEF/PCR-RFLP techniques. The result clearly shows by using SPE and TIC techniques only 35.85 % and 50.08% of ...

Cloning of truncation variants of α1-antitrypsin

Introduction Alpha1-antitrypsin is a member of the serpin (serine protease inhibitor) family of proteins . It controls the breakdown of elastic tissue in the lung by inhibiting human neutrophil elastase. It does so by the remarkable serpin mechanism forming a covalent complex with the enzyme and undergoing a dramatic, stabilising conformational change in order to fully disable it . However this...

Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy.

Endoplasmic reticulum-associated degradation (ERAD) and autophagy cooperate to degrade polymerogenic mutant serpins.

The serpinopathies are a family of diseases characterized by the accumulation of ordered polymers of mutant protein within the endoplasmic reticulum. They are a diverse group including alpha(1)-antitrypsin deficiency and the inherited dementia familial encephalopathy with neuroserpin inclusion bodies or FENIB. We have used transient transfection of COS7 cells and mouse embryonic fibroblasts, PC...