摘要
本文就p53上调的凋亡介质(PUMA)在分子通路中的作用及其潜在的治疗应用方面的研究进展作一综述。特别强调了PUMA在电离辐射诱导信号传递中的作用,因为正常组织的放射毒性主要是通过细胞凋亡介导的。本文介绍了Puma及其对P53的依赖和不依赖p53的诱导作用,并对其作为发展辐射防护剂的新靶点提出了建议。进一步的影响,包括针对PUMA预防和治疗心血管和神经退行性疾病,并结合其他治疗应用的概述。最后介绍了新型PUMA调节剂的基本化学结构,如哌啶衍生物、激酶抑制剂或Bcl-2蛋白家族的调节剂。
关键词: PUMA,电离辐射,小分子抑制剂,辐射防护,炉膛,脑。
图形摘要
Current Drug Targets
Title:New Light on An Old Friend: Targeting PUMA in Radioprotection and Therapy of Cardiovascular and Neurodegenerative Diseases
Volume: 19 Issue: 16
关键词: PUMA,电离辐射,小分子抑制剂,辐射防护,炉膛,脑。
摘要: This review summarizes recent progress in understanding the role of p53-upregulated mediator of apoptosis (PUMA) in molecular pathways with respect to its potential therapeutic applications. Particular emphasis is given to the PUMA´s role in ionizing radiation-induced signalling as radiotoxicity of normal tissue is mediated mostly via apoptosis. PUMA and its p53-dependent and p53- independent induction are described and potential use as a new target for the development of radioprotective agents is suggested. Further implications, including targeting PUMA to prevent and treat cardiovascular and neurodegenerative diseases, are also discussed together with an overview of other therapeutic applications. Finally, basic chemical structures for the development of novel PUMA modulators such as pifithrine derivatives, kinase inhibitors or modulators of Bcl-2 protein family are described.
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Cite this article as:
New Light on An Old Friend: Targeting PUMA in Radioprotection and Therapy of Cardiovascular and Neurodegenerative Diseases, Current Drug Targets 2018; 19 (16) . https://dx.doi.org/10.2174/1389450119666180406110743
DOI https://dx.doi.org/10.2174/1389450119666180406110743 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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