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p38 丝裂原活化蛋白激酶在 COPD 中的作用:病理生物学意义和治疗展望。

Role of p38-mitogen-activated protein kinase in COPD: pathobiological implications and therapeutic perspectives.

机构信息

Department of Health Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.

Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy.

出版信息

Expert Rev Respir Med. 2020 May;14(5):485-491. doi: 10.1080/17476348.2020.1732821. Epub 2020 Feb 24.

DOI:10.1080/17476348.2020.1732821
PMID:32077346
Abstract

: The p38 serine-threonine kinases are members of the large family of mitogen-activated protein kinases (MAPK). In particular, p38 MAPK subgroup includes four isoforms (α, β, γ, δ), among which p38α and p38β are mainly involved in inflammatory disorders. Indeed, by activating key transcription factors and by inducing the expression of several cytokines and chemokines, p38α plays a central role in the pathobiology of chronic obstructive pulmonary disease (COPD).: This concise review focuses on the contribution of p38 MAPK to development, maintenance, and amplification of chronic lung inflammation in COPD. Moreover, we discuss the potential role of p38 MAPK as suitable target for perspective therapeutic approaches under evaluation as potential new COPD treatments. In this regard, an extensive literature search has been conducted throughout PubMed source (1990-2020).: Despite some promising preclinical data, so far the results of clinical trials evaluating p38 MAPK inhibitors have been quite disappointing, thus suggesting a cautious judgment about the future perspectives of these drugs for COPD therapy.

摘要

p38 丝氨酸-苏氨酸激酶是丝裂原活化蛋白激酶(MAPK)大家族的成员。特别是,p38 MAPK 亚组包括四个同工型(α、β、γ、δ),其中 p38α 和 p38β 主要参与炎症性疾病。事实上,p38α 通过激活关键转录因子并诱导几种细胞因子和趋化因子的表达,在慢性阻塞性肺疾病(COPD)的病理生物学中发挥核心作用。

这篇简洁的综述重点介绍了 p38 MAPK 对 COPD 中慢性肺炎症的发展、维持和放大的贡献。此外,我们还讨论了 p38 MAPK 作为有前途的治疗靶点的潜在作用,这些靶点正在评估中,作为潜在的新 COPD 治疗方法。在这方面,已经通过 PubMed 资源(1990-2020 年)进行了广泛的文献检索。

尽管有一些有前途的临床前数据,但迄今为止评估 p38 MAPK 抑制剂的临床试验结果相当令人失望,因此对这些药物在 COPD 治疗中的未来前景需要谨慎判断。

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