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Kim SJ Lee BH Lee YS Kang KS 《Biochemical and biophysical research communications》2007,360(3):593-599
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. 相似文献
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Stepwise assembly of functional C‐terminal REST/NRSF transcriptional repressor complexes as a drug target 下载免费PDF全文
Ken Inui Zongpei Zhao Juan Yuan Sakthidasan Jayaprakash Le T. M. Le Srdja Drakulic Bjoern Sander Monika M. Golas 《Protein science : a publication of the Protein Society》2017,26(5):997-1011