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

Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy
Department of Experimental Medicine, University of Perugia, 06123 Perugia, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2365;
Received: 22 March 2019 / Revised: 3 May 2019 / Accepted: 7 May 2019 / Published: 13 May 2019
(This article belongs to the Special Issue Neuroprotective Strategies 2019)
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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. View Full-Text
Keywords: Niemann-Pick type A disease; neutral sphingomyelinase; vitamin D receptor; Toll-like receptors Niemann-Pick type A disease; neutral sphingomyelinase; vitamin D receptor; Toll-like receptors

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Conte, C.; Arcuri, C.; Cataldi, S.; Mecca, C.; Codini, M.; Ceccarini, M.R.; Patria, F.F.; Beccari, T.; Albi, E. Niemann-Pick Type A Disease: Behavior of Neutral Sphingomyelinase and Vitamin D Receptor. Int. J. Mol. Sci. 2019, 20, 2365.

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