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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Wiley
2017-01-01
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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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id | doaj-art-cabeb2e83b074574baa04ccd87b23e9e |
institution | Kabale University |
issn | 0953-4180 1875-8584 |
language | English |
publishDate | 2017-01-01 |
publisher | Wiley |
record_format | Article |
series | Behavioural Neurology |
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 |
work_keys_str_mv | AT oycalhan micewithcatalyticallyinactivecathepsinadisplayneurobehavioralalterations AT vseyrantepe micewithcatalyticallyinactivecathepsinadisplayneurobehavioralalterations |