Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations

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 dise...

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Main Authors: O. Y. Calhan, V. Seyrantepe
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Behavioural Neurology
Online Access:http://dx.doi.org/10.1155/2017/4261873
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author O. Y. Calhan
V. Seyrantepe
author_facet O. Y. Calhan
V. Seyrantepe
author_sort O. Y. Calhan
collection DOAJ
description 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.
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spelling doaj-art-cabeb2e83b074574baa04ccd87b23e9e2025-02-03T06:00:14ZengWileyBehavioural Neurology0953-41801875-85842017-01-01201710.1155/2017/42618734261873Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral AlterationsO. Y. Calhan0V. Seyrantepe1Department of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce Mahallesi, Urla, Izmir, TurkeyDepartment of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce Mahallesi, Urla, Izmir, TurkeyThe 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.http://dx.doi.org/10.1155/2017/4261873
spellingShingle O. Y. Calhan
V. Seyrantepe
Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations
Behavioural Neurology
title Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations
title_full Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations
title_fullStr Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations
title_full_unstemmed Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations
title_short Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations
title_sort mice with catalytically inactive cathepsin a display neurobehavioral alterations
url http://dx.doi.org/10.1155/2017/4261873
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AT vseyrantepe micewithcatalyticallyinactivecathepsinadisplayneurobehavioralalterations