title: Mice with Catalytically Inactive Cathepsin A Display Neurobehavioral Alterations.
abstract: The lysosomal carboxypeptidase A, Cathepsin A (CathA), is a serine protease with two distinct functions. CathA protectsβ-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 inCathAS190Amice, 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.
authors.affiliation: Department of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce Mahallesi, Urla, Izmir, Turkey.
authors.forename: O Y
authors.initials: OY
authors.lastname: Calhan
authors.affiliation: Department of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce Mahallesi, Urla, Izmir, Turkey.
authors.forename: V
authors.identifier: 0000-0002-0243-5011
authors.initials: V
authors.lastname: Seyrantepe
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D043402:Cathepsin A / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008297:Male; D000069077:Memory Consolidation / Q000502:physiology; D008569:Memory Disorders / Q000201:enzymology / Q000378:metabolism*; D057567:Memory, Long-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010121:Oxytocin / Q000378:metabolism*; D065852:Spatial Memory / Q000502:physiology
chemical_list: D019332:Endothelin-1; D010121:Oxytocin; D043402:Cathepsin A