Inhibition of CatA: an emerging strategy for the treatment of heart failure. (March 2013)

• Record Type: Journal Article
• Authors: Ruf, Sven; Buning, Christian; Schreuder, Herman; Linz, Wolfgang; Hübschle, Thomas; Linz, Dominik; Ruetten, Hartmut; Wirth, Klaus; Sadowski, Thorsten
• Is Part Of: Future medicinal chemistry. Volume 5:Number 4(2013)
• Page Start: 399
• Page End: 409
• Publication Date: 2013-03
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc.13.24
• Languages: English
• ISSNs: 1756-8919

Abstract

The lysosomal serine carboxypeptidase CatA has a very important and well-known structural function as well as a, so far, less explored catalytic function. A complete loss of the CatA protein results in the lysosomal storage disease galactosialidosis caused by intralysosomal degradation of β-galactosidase and neuraminidase 1. However, mice with a catalytically inactive CatA enzyme show no signs of this disease. This observation establishes a clear distinction between structural and catalytic functions of the CatA enzyme. Recently, several classes of orally bioavailable synthetic inhibitors of CatA have been identified. Pharmacological studies in rodents indicate a remarkable influence of CatA inhibition on cardiovascular disease progression and identify CatA as a promising novel target for the treatment of heart failure.