Abstract:

In the early '90s, seminal work on rodent liver demonstrated that the hypolipidemic effect of xenobiotics, referred to as peroxisome proliferators, was mediated by a member of steroid hormone receptor superfamily, thus designated peroxisome proliferator-activated receptors (PPARs). The research field opened by this discovery led to the identification of three isotypes, namely PPARα (NR1C1), PPARβ/δ (NR1C2), PPARγ (NR1C3), in a wide range of tissues. All these receptors act as ligand-activated transcription factors, binding lipid molecules with different, though overlapping, specificity. PPARs, as other members of the nuclear receptor superfamily, comprise four domains - one of which binds to specific DNA sequences (PPAR response elements, PPREs) - regulating gene expression as heterodimers with retinoid X receptors (RXRs). PPAR activity is modulated by post-translational modifications, such as phosphorylation, SUMOylation, ubiquitylation, and by several corepressors and coactivators. It is now well established that PPARs act as lipid sensors, playing a major role in energy homeostasis, lipid metabolism and ROS production/scavenging, thus being involved in key cell processes, including cell proliferation, death and differentiation. These receptors are regulators of oxidative stress, inflammation and immune response, making them a suitable target for the treatment of chronic inflammatory diseases, diabetes, cancer and neurodegenerative disorders.90年代早期，在啮齿动物肝脏中的开创性工作证明了异生素的降血脂作用，即过氧化物酶体增殖是由类固醇激素受体超家族成员介导的，因而出现了过氧化物酶体增殖物激活受体（PPARs）。这一研究领域的发现引出了三个同种型受体，即PPARα（NR1C1），PPARβ/δ（NR1C2），PPARγ（NR1C3）。所有这些受体均为充当配体活化的转录因子，结合不同的脂质分子虽有重叠但各具特异性。意大利罗马第三大学Sandra Moreno教授在发表于《中国神经再生研究（英文版）》杂志2015年9月第9期的观点文章中主要介绍了PPARs——核受体超家族的其他成员，PPAR活性是通过转译后修饰的，如磷酸化，SUMO化，泛素化调制，以及由几个辅阻遏物的共激活因子。现在公认的是PPARs可作为脂质传感器，在能量稳态，脂质代谢和ROS产生/清除中起到主要作用，也因此被卷入关键细胞过程，包括细胞增殖，死亡和分化。这些受体是氧化应激，炎症和免疫反应的调节因素，并使之成为一个用于治疗慢性炎症疾病，糖尿病，癌症和神经退行性疾病治疗的合适靶标。Article: "In search for novel strategies towards neuroprotection and neuroregeneration: is PPARα a promising therapeutic target?" by Sandra Moreno1, Maria Paola Cerù1,2 (1 Department of Science-LIME, University Roma Tre, Rome, Italy 2 Department of Life, Health and Environmental Sciences, University of L’Aquila, Coppito (AQ), Italy). Moreno S, Cerù MP (2015) In search for novel strategies towards neuroprotection and neuroregeneration: is PPARα a promising therapeutic target? Neural Regen Res 10(9):1409-1412. 欲获更多资讯：请与《中国神经再生研究（英文版）》杂志国际发展部联络；联络电话：+8613804998773，或用电子邮件联络：eic@nrren.org。 文章全文请见：http://www.nrronline.org/