S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Journal Papers (저널논문_수의학과)
Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann–Pick type C disease improved by valproic acid, a histone deacetylase inhibitor
- Kim, Sun-Jung; Lee, Bong-Hee; Lee, Yong Soon; Kang, Kyung-Sun
- Issue Date
- Biochem. Biophys. Res. Commun. 360 (2007) 593-599
- Niemann–Pick type C disease; Neural stem cells; Valproic acids; A histone deacetylase inhibitor
- 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.
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