NDLI: (+)-Cholesten-3-one induces differentiation of neural stem cells into dopaminergic neurons through BMP signaling.

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(+)-Cholesten-3-one induces differentiation of neural stem cells into dopaminergic neurons through BMP signaling.

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(+)-Cholesten-3-one induces differentiation of neural stem cells into dopaminergic neurons through BMP signaling.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chen, Dong-Feng Meng, Ling-Jie Du, Shao-Hui Zhang, Hai-Ling Li, Hui Zhou, Jian-Hong Li, Yi-Wei Zeng, He-Ping Hua, Zi-Chun
Description	Country affiliation: China Author Affiliation: Chen DF ( The State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing, China. CDF27212@21cn.com)
Abstract	To identify small molecules that induce dopaminergic neurons from neural stem cells (NSCs) is promising for therapy of Parkinson's disease. Here we report the results of analyzing structurally related steroids in traditional Chinese medicine to identify agents that enhance dopaminergic differentiation of NSCs. Using P19 cells transfected by tyrosine hydroxylase (TH) promoter reporter construct, (+)-Cholesten-3-one with carbonyl, but not cholesterol and cholesterol myristate can effectively promote the activity of TH promoter. This effect depends on bone morphogenetic protein (BMP) signaling. Phenotypic cellular analysis indicated that (+)-Cholesten-3-one induces differentiation of NSCs to dopaminergic neurons with increased expression of specific dopaminergic markers including TH, dopamine transporter, dopa decarboxylase and higher level of dopamine secretion. (+)-Cholesten-3-one significantly increases the expression of BMPR IB, but not BMPR IA or BMPR II; p-Smad1/5/8 positive nuclei and expression of p-Smad1/5/8 were detected in NSCs treated with (+)-Cholesten-3-one, indicating that (+)-Cholesten-3-one may activate the BMP signaling. Moreover, overexpression of BMP4 or inhibition of BMP affects the effect of (+)-Cholesten-3-one on the dopaminergic phenotype. These findings may contribute to efficient production of dopaminergic neurons from NSCs culture for many applications and raise interesting questions about the role of (+)-Cholesten-3-one in neurogenesis.
File Format	HTM / HTML
ISSN	01680102
Issue Number	3
Volume Number	68
e-ISSN	18728111
Journal	Neuroscience Research
Language	English
Publisher	Elsevier
Publisher Date	2010-11-01
Publisher Place	Ireland
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Neurology Bone Morphogenetic Proteins Metabolism Cholestenones Dopamine Neural Stem Cells Physiology Neurogenesis Neurons Analysis Of Variance Animals Blotting, Western Cell Line Cells, Cultured Chromatography, High Pressure Liquid Flow Cytometry Immunohistochemistry Cytology Promoter Regions, Genetic Rats Rats, Sprague-dawley Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Transfection Tyrosine 3-monooxygenase Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Neuroscience Medicine

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(+)-Cholesten-3-one induces differentiation of neural stem cells into dopaminergic neurons through BMP signaling.

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