Rosiglitazone activation of PPAR gamma-dependent pathways is neuroprotective in human neural stem cells against amyloid-beta-induced mitochondrial dysfunction and oxidative stress

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题名:	Rosiglitazone activation of PPAR gamma-dependent pathways is neuroprotective in human neural stem cells against amyloid-beta-induced mitochondrial dysfunction and oxidative stress
作者:	Chiang, MC (Chiang, Ming-Chang) Nicol, CJ (Nicol, Christopher J.) Cheng, YC (Cheng, Yi-Chuan) Lin, KH (Lin, Kuan-Hung) Yen, CH (Yen, Chia-Hui) Lin, CH (Lin, Chien-Hung)
贡献者:	生科所
关键词:	PPAR gamma PGC1 alpha hNSCs A beta
日期:	2016-04
上传时间:	2017-04-14 13:48:18 (UTC+8)
摘要:	Neuronal cell impairment, such as that induced by amyloid-beta (A beta) protein, is a process with limited therapeutic interventions and often leads to long-term neurodegeneration common in disorders such as Alzheimer's disease. Interestingly, peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated nuclear receptor whose ligands control many physiological and pathologic processes, and may be neuroprotective. We hypothesized that rosiglitazone, a PPAR gamma agonist, would prevent A beta-mediated effects in human neural stem cells (hNSCs). Here, we show that rosiglitazone reverses, via PPAR gamma-dependent downregulation of caspase 3 and 9 activity, the A beta-mediated decreases in hNSC cell viability. In addition, A beta decreases hNSC messenger RNA (mRNA) levels of 2 neuroprotective factors (Bcl-2 and CREB), but co-treatment with rosiglitazone significantly rescues these effects. Rosiglitazone co-treated hNSCs also showed significantly increased mitochondrial function (reflected by levels of adenosine triphosphate and Mit mass), and PPAR gamma-dependent mRNA upregulation of PGC1 alpha and mitochondrial genes (nuclear respiratory factor-1 and Tfam). Furthermore, hNSCs co-treated with rosiglitazone were significantly rescued from A beta-induced oxidative stress and correlates with reversal of the A beta-induced mRNA decrease in oxidative defense genes (superoxide dismutase 1, superoxide dismutase 2, and glutathione peroxidase 1). Taken together, these novel findings show that rosiglitazone-induced activation of PPAR gamma-dependent signaling rescues A beta-mediated toxicity in hNSCs and provide evidence supporting a neuroprotective role for PPAR gamma activating drugs in A beta-related diseases such as Alzheimer's disease. (C) 2016 Elsevier Inc. All rights reserved.
關聯:	NEUROBIOLOGY OF AGING 卷: 40 頁碼: 181-190
显示于类别:	[生物科技研究所 ] 期刊論文

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