Dr. B. R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi 110007, India.
Eur J Clin Microbiol Infect Dis. 2011 Apr;30(4):483-98. doi: 10.1007/s10096-010-1122-9. Epub 2010 Dec 9.
Cerebral malaria (CM) is a global life-threatening complication of Plasmodium infection and represents a major cause of morbidity and mortality among severe forms of malaria. Despite developing knowledge in understanding mechanisms of pathogenesis, the current anti-malarial agents are not sufficient due to drug resistance and various adverse effects. Therefore, there is an urgent need for the novel target and additional therapy. Recently, peroxisome proliferator-activated receptor (PPAR) a nuclear receptors (NR) and agonists of its isoforms (PPARγ, PPARα and PPARβ/δ) have been demonstrated to exhibit anti-inflammatory and immunomodulatory properties, which are driven to a new approach of research on inflammatory diseases. Although many studies on PPARs have confirmed their diverse biological role, there is a lack of knowledge of its therapeutic use in CM. The major objective of this review is to explore the possible experimental studies to link these two areas of research. We focus on the data describing the beneficial effects of this receptor in inflammation, which is observed as a basic pathology in CM. In conclusion, PPARs could be a novel target in treating inflammatory diseases, and continued work with the available and additional agonists screened from various sources may result in a potential new treatment for CM.
脑型疟疾(CM)是一种全球性的危及生命的疟疾感染并发症,是严重疟疾的主要发病率和死亡率原因之一。尽管在了解发病机制方面有了一定的认识,但由于药物耐药性和各种不良反应,目前的抗疟药物还不够。因此,迫切需要新的靶点和额外的治疗方法。最近,过氧化物酶体增殖物激活受体(PPAR)核受体(NR)及其同工型激动剂(PPARγ、PPARα 和 PPARβ/δ)已被证明具有抗炎和免疫调节特性,这为炎症性疾病的研究提供了一种新的方法。尽管许多关于 PPAR 的研究已经证实了它们的多种生物学作用,但对于其在 CM 中的治疗用途的了解还很缺乏。本综述的主要目的是探讨将这两个研究领域联系起来的可能的实验研究。我们重点介绍描述该受体在炎症中有益作用的数据,因为炎症是 CM 的基本病理学。总之,PPAR 可能是治疗炎症性疾病的一个新靶点,继续使用各种来源筛选出的现有和额外激动剂可能会为 CM 带来一种潜在的新治疗方法。