Alpha₁-Antitrypsin Deficiency — A Model for Conformational Diseases

Alpha1-antitrypsin is a member of a family of protease inhibitors known as the serpins. Mutations in these molecules can lead to disease, not only because the biologic activity of the protease in tissue is increased, but also because the mutations result in misfolded (i.e., conformationally abnormal) protease molecules that accumulate in tissue. This review article summarizes the action of these protease inhibitors and how mutations lead to their accumulation in particular neurodegenerative disorders such as prion encephalopathies and Alzheimer's disease.