Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations

Abstract EN

The lysosomal carboxypeptidase A, Cathepsin A (CathA), is a serine protease with two distinct functions.

CathA protects β-galactosidase and sialidase Neu1 against proteolytic degradation by forming a multienzyme complex and activates sialidase Neu1.

CathA deficiency causes the lysosomal storage disease, galactosialidosis.

These patients present with a broad range of clinical phenotypes, including growth retardation, and neurological deterioration along with the accumulation of the vasoactive peptide, endothelin-1, in the brain.

Previous in vitro studies have shown that CathA has specific activity against vasoactive peptides and neuropeptides, including endothelin-1 and oxytocin.

A mutant mouse with catalytically inactive CathA enzyme (CathAS190A) shows increased levels of endothelin-1.

In the present study, we elucidated the involvement of CathA in learning and long-term memory in 3-, 6-, and 12-month-old mice.

Hippocampal endothelin-1 and oxytocin accumulated in CathAS190A mice, which showed learning impairments as well as long-term and spatial memory deficits compared with wild-type littermates, suggesting that CathA plays a significant role in learning and in memory consolidation through its regulatory role in vasoactive peptide processing.