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Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann–Pick type C disease improved by valproic acid, a histone deacetylase inhibitor

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Authors
Kim, Sun-Jung; Lee, Bong-Hee; Lee, Yong Soon; Kang, Kyung-Sun
Issue Date
2007-07-02
Publisher
Elsevier
Citation
Biochem. Biophys. Res. Commun. 360 (2007) 593-599
Keywords
Niemann–Pick type C diseaseNeural stem cellsValproic acidsA histone deacetylase inhibitor
Abstract
Niemann–Pick type C disease (NPC) is a neurodegenerative and lipid storage disorder for which no effective treatment is known. We previously reported that neural stem cells derived from NPC1 mice showed impaired self-renewal and differentiation. We examined whether valproic acid (VPA), a histone deacetylase inhibitor, could enhance neuronal differentiation and recover defective cholesterol metabolism in neural stem cells (NSCs) from NPC1-deficient mice (NPC1−/−). VPA could induce neuronal differentiation and restore impaired astrocytes in NSCs from NPC1−/− mice. Importantly, an increasing level of cholesterol within NSCs from NPC1−/− mice could be reduced by VPA. Moreover, essential neurotrophic genes (TrkB, BDNF, MnSoD, and NeuroD) were up-regulated through the repression of the REST/NRSF and HDAC complex by the VPA treatment. Up-regulated neurotrophic genes were able to enhance neural differentiation and cholesterol homeostasis in neural stem cells from NPC1−/− mice. In this study, we suggested that, along with cholesterol homeostasis, impaired neuronal differentiation and abnormal morphology of astrocytes could be rescued by the inhibition of HDAC and REST/NRSF activity induced by VPA treatment.
ISSN
0006-291X
Language
English
URI
http://hdl.handle.net/10371/6960
DOI
https://doi.org/10.1016/j.bbrc.2007.06.116
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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