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Behavioural Neurology
Volume 2017, Article ID 4261873, 11 pages
https://doi.org/10.1155/2017/4261873
Research Article

Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations

Department of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce Mahallesi, Urla, Izmir, Turkey

Correspondence should be addressed to V. Seyrantepe; rt.ude.etyi@epetnaryesnaklov

Received 9 September 2016; Accepted 5 December 2016; Published 4 January 2017

Academic Editor: Barbara Picconi

Copyright © 2017 O. Y. Calhan and V. Seyrantepe. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 () 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 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.