Yi Jae-Hyuk, Park Seung-Won, Kapadia Ramya, Vemuganti Raghu
Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA.
Neurochem Int. 2007 Jun;50(7-8):1014-27. doi: 10.1016/j.neuint.2007.04.019. Epub 2007 May 3.
Inflammation is a known precipitator of neuronal death after cerebral ischemia. The mechanisms that promote or curtail the start and spread of inflammation in brain are still being debated. By virtue of their capability to modulate gene expression, several transcription factors induced in the ischemic brain can modulate the post-ischemic inflammation. While the induction of transcription factors such as IRF1, NF-kappaB, ATF-2, STAT3, Egr1 and C/EBPbeta is thought to promote post-ischemic inflammation, activation of transcription factors such as HIF-1, CREB, c-fos, PPARalpha, PPARgamma and p53 is thought to prevent post-ischemic inflammation and neuronal damage. Of these, PPARgamma which is a ligand-activated transcription factor was recently shown to prevent inflammatory gene expression in several animal models CNS disorders. This review article discusses some of the molecular mechanisms of PPARgamma induction by its agonists following focal cerebral ischemia.
炎症是脑缺血后神经元死亡的已知诱因。促进或抑制脑部炎症起始和扩散的机制仍在争论之中。凭借其调节基因表达的能力,缺血性脑中诱导产生的几种转录因子可调节缺血后炎症。虽然诸如IRF1、NF-κB、ATF-2、STAT3、Egr1和C/EBPβ等转录因子的诱导被认为会促进缺血后炎症,但诸如HIF-1、CREB、c-fos、PPARα、PPARγ和p53等转录因子的激活被认为可预防缺血后炎症和神经元损伤。其中,PPARγ作为一种配体激活的转录因子,最近在几种动物模型的中枢神经系统疾病中被证明可预防炎症基因表达。这篇综述文章讨论了局灶性脑缺血后其激动剂诱导PPARγ的一些分子机制。