Koller Garrit, Schlomann Uwe, Golfi Panagiota, Ferdous Taheera, Naus Silvia, Bartsch Jörg W
King's College London, Department of Biochemistry, London, United Kingdom.
Curr Pharm Des. 2009;15(20):2272-81. doi: 10.2174/138161209788682361.
While it is highly accepted that ADAM family members with ubiquitous expression patterns, such as ADAM10 and ADAM17 have major roles in homoeostasis and pathology, ADAM8 was initially considered as an immune-specific ADAM with a cell-specific expression pattern. Therefore, ADAM8 had a "sleeping beauty" existence for many years, and has recently come back into focus as it was detected under several pathological conditions. These were found to typically involve inflammation and remodelling of the extracellular matrix, including cancers and serious respiratory diseases such as asthma. In these diseases, induced expression of ADAM8 by different stimuli results in cleavage of various substrates, including cell adhesion molecules, cytokine receptors, and ECM components. Involvement of ADAM8 in individual diseases indicates its usefulness as both a diagnostic and prognostic marker. Even more strikingly, as ADAM8 progressively emerges as a key effector in pathological processes, so does its attractiveness as a therapeutic target rather than being a mere indicator of disease and its progression. This is encouraged by analysis of ADAM8 null mice, identifying no adverse phenotype in the absence of functional ADAM8. Thus, ADAM8 potentially is an attractive drug target in a variety of diseases. In this review, the current knowledge on ADAM8 in diseases and avenues for specific inhibition based on unique biochemical features of ADAM8 will be presented.
虽然人们普遍认为具有广泛表达模式的ADAM家族成员，如ADAM10和ADAM17在体内平衡和病理学中起主要作用，但ADAM8最初被认为是一种具有细胞特异性表达模式的免疫特异性ADAM。因此，ADAM8多年来一直处于“沉睡”状态，直到最近在几种病理条件下被检测到，它才重新成为焦点。这些病理条件通常涉及炎症和细胞外基质重塑，包括癌症和严重的呼吸系统疾病，如哮喘。在这些疾病中，不同刺激诱导ADAM8表达会导致各种底物的裂解，包括细胞粘附分子、细胞因子受体和细胞外基质成分。ADAM8参与个体疾病表明它作为诊断和预后标志物的有用性。更引人注目的是，随着ADAM8逐渐成为病理过程中的关键效应因子，它作为治疗靶点的吸引力也在增加，而不仅仅是疾病及其进展的指标。对ADAM8基因敲除小鼠的分析支持了这一点，该分析表明在缺乏功能性ADAM8的情况下没有不良表型。因此，ADAM8在多种疾病中可能是一个有吸引力的药物靶点。在这篇综述中，将介绍目前关于ADAM8在疾病中的知识以及基于ADAM8独特生化特性的特异性抑制途径。
