过氧化物酶体增殖物激活受体(PPARα,-β/δ和-γ)是脂质激活的转录因子。合成的PPARα和PPARγ配体具有神经保护特性。最近,PPARβ/δ激活成为治疗多种神经退行性疾病的新方法的焦点。为了填补有关PPARβ/δ在大脑中的作用的知识空白,需要有关PPARβ/δ参与神经病理过程的新假设。在本文中,我们描述了一个新的假设,声称三种PPAR同种型之间存在紧密相互作用,我们称之为“PPAR三合会”。我们认为PPARβ/δ对PPAR三联体具有中央控制作用。大多数研究仅分析PPAR同种型之一的调节。一些报道描述了PPAR激动剂对所有三种PPAR同种型的表达水平的相互调节。对描述了PPAR成对相互作用的这些研究的分析使我们能够支持对PPARβ/δ具有核心作用的PPAR三联体的存在。在本次审查中,我们提出了一个假设,在广泛的脑部疾病中,PPARβ/δ在PPARα和PPARγ中起重要作用。最后,我们通过描述PPARβ/δ参与髓鞘形成调节的假设来证明PPAR三联体概念的优势,谷氨酸诱导的神经毒性,以及活性氧/NO/Ca(2+)的信号通路。
Peroxisome proliferator-activated receptors (PPARα, -β/δ and -γ) are lipid-activated transcription factors. Synthetic PPARα and PPARγ ligands have neuroprotective properties. Recently, PPARβ/δ activation emerged as the focus of a novel approach for the treatment of a wide range of neurodegenerative diseases. To fill the gap of knowledge about the role of PPARβ/δ in brain, new hypotheses about PPARβ/δ involvement in neuropathological processes are requested. In this paper, we describe a novel hypothesis, claiming the existence of tight interactions between the three PPAR isotypes, which we designate the \"PPAR triad\". We propose that PPARβ/δ has a central control of the PPAR triad. The majority of studies analyze the regulation only by one of the PPAR isotypes. A few reports describe the mutual regulation of expression levels of all three PPAR isotypes by PPAR agonists. Analysis of these studies where pairwise interactions of PPARs were described allows us to support the existence of the PPAR triad with central role for PPARβ/δ. In the present
review, we propose the hypothesis that in a wide range of brain disorders, PPARβ/δ plays a central role between PPARα and PPARγ. Finally, we prove the advantages of the PPAR triad concept by describing hypotheses of PPARβ/δ involvement in the regulation of myelination, glutamate-induced neurotoxicity, and signaling pathways of reactive oxygen species/NO/Ca(2+).