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Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor

Sphingomyelinase (SMase) is responsible for the breakdown of sphingomyelin (SM) with production of ceramide. The absence of acid sphingomyelinase (aSMase) causes abnormal synapse formation in Niemann-Pick type A (NPA) disease. Because high levels of ceramide in the NPA brain were demonstrated, the i...

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Autores principales: Conte, Carmela, Arcuri, Cataldo, Cataldi, Samuela, Mecca, Carmen, Codini, Michela, Ceccarini, Maria Rachele, Patria, Federica Filomena, Beccari, Tommaso, Albi, Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539364/
https://www.ncbi.nlm.nih.gov/pubmed/31086057
http://dx.doi.org/10.3390/ijms20092365
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author Conte, Carmela
Arcuri, Cataldo
Cataldi, Samuela
Mecca, Carmen
Codini, Michela
Ceccarini, Maria Rachele
Patria, Federica Filomena
Beccari, Tommaso
Albi, Elisabetta
author_facet Conte, Carmela
Arcuri, Cataldo
Cataldi, Samuela
Mecca, Carmen
Codini, Michela
Ceccarini, Maria Rachele
Patria, Federica Filomena
Beccari, Tommaso
Albi, Elisabetta
author_sort Conte, Carmela
collection PubMed
description Sphingomyelinase (SMase) is responsible for the breakdown of sphingomyelin (SM) with production of ceramide. The absence of acid sphingomyelinase (aSMase) causes abnormal synapse formation in Niemann-Pick type A (NPA) disease. Because high levels of ceramide in the NPA brain were demonstrated, the involvement of other SMases were supposed. In the present study we focused the attention on the neurogenic niches in the hippocampal gyrus dentatus (GD), a brain structure essential for forming cohesive memory. We demonstrated for the first time the increase of (Sex determining region Y)-box 2 (SOX2), and the down-regulation of glial fibrillary acidic protein (GFAP) NPA mice GD. Moreover, we found that the expression of Toll like receptors (TLRs), was increased in NPA mice, particularly TLR2, TLR7, TLR8 and TLR9 members. Although no significant change in neutral sphingomyelinase (nSMase) gene expression was detected in the NPA mice hippocampus of, protein levels were enhanced, probably because of the slower protein degradation rate in this area. Many studies demonstrated that vitamin D receptor (VDR) is expressed in the hippocampus GD. Unexpectedly, we showed that NPA mice exhibited VDR gene and protein expression up-regulation. In summary, our study suggests a relation between hippocampal cell differentiation defect, nSMase and VDR increase in NPA mice.
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spelling pubmed-65393642019-06-04 Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor Conte, Carmela Arcuri, Cataldo Cataldi, Samuela Mecca, Carmen Codini, Michela Ceccarini, Maria Rachele Patria, Federica Filomena Beccari, Tommaso Albi, Elisabetta Int J Mol Sci Article Sphingomyelinase (SMase) is responsible for the breakdown of sphingomyelin (SM) with production of ceramide. The absence of acid sphingomyelinase (aSMase) causes abnormal synapse formation in Niemann-Pick type A (NPA) disease. Because high levels of ceramide in the NPA brain were demonstrated, the involvement of other SMases were supposed. In the present study we focused the attention on the neurogenic niches in the hippocampal gyrus dentatus (GD), a brain structure essential for forming cohesive memory. We demonstrated for the first time the increase of (Sex determining region Y)-box 2 (SOX2), and the down-regulation of glial fibrillary acidic protein (GFAP) NPA mice GD. Moreover, we found that the expression of Toll like receptors (TLRs), was increased in NPA mice, particularly TLR2, TLR7, TLR8 and TLR9 members. Although no significant change in neutral sphingomyelinase (nSMase) gene expression was detected in the NPA mice hippocampus of, protein levels were enhanced, probably because of the slower protein degradation rate in this area. Many studies demonstrated that vitamin D receptor (VDR) is expressed in the hippocampus GD. Unexpectedly, we showed that NPA mice exhibited VDR gene and protein expression up-regulation. In summary, our study suggests a relation between hippocampal cell differentiation defect, nSMase and VDR increase in NPA mice. MDPI 2019-05-13 /pmc/articles/PMC6539364/ /pubmed/31086057 http://dx.doi.org/10.3390/ijms20092365 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Conte, Carmela
Arcuri, Cataldo
Cataldi, Samuela
Mecca, Carmen
Codini, Michela
Ceccarini, Maria Rachele
Patria, Federica Filomena
Beccari, Tommaso
Albi, Elisabetta
Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor
title Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor
title_full Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor
title_fullStr Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor
title_full_unstemmed Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor
title_short Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor
title_sort niemann-pick type a disease: behavior of neutral sphingomyelinase and vitamin d receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539364/
https://www.ncbi.nlm.nih.gov/pubmed/31086057
http://dx.doi.org/10.3390/ijms20092365
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