Rigby Rachel E, Leitch Andrea, Jackson Andrew P
MRC Human Genetics Unit, Western General Hospital, Edinburgh EH42XU, UK.
Bioessays. 2008 Sep;30(9):833-42. doi: 10.1002/bies.20808.
Enzymes that degrade nucleic acids are emerging as important players in the pathogenesis of inflammatory disease. This is exemplified by the recent identification of four genes that cause the childhood inflammatory disorder, Aicardi-Goutières syndrome (AGS). This is an autosomal recessive neurological condition whose clinical and immunological features parallel those of congenital viral infection. The four AGS genes encode two nucleases: TREX1 and the hetero-trimeric Ribonuclease H2 (RNase H2) complex. The biochemical activity of these enzymes was initially characterised 30 years ago but a role in neurological inflammation was entirely unanticipated until they were found to be mutated in AGS. This has led to a hypothesis that accumulation of intracellular nucleic acids occurs as a consequence of mutation in these enzymes and triggers an inflammatory response through activation of innate immune pattern recognition receptors.
降解核酸的酶正成为炎症性疾病发病机制中的重要因素。最近鉴定出的四个导致儿童炎症性疾病——艾卡迪-古铁雷斯综合征（AGS）的基因就是例证。这是一种常染色体隐性神经疾病，其临床和免疫学特征与先天性病毒感染相似。四个AGS基因编码两种核酸酶：TREX1和异源三聚体核糖核酸酶H2（RNase H2）复合物。这些酶的生化活性最初是在30年前得到表征的，但直到发现它们在AGS中发生突变，才完全预料到它们在神经炎症中的作用。这引发了一种假说，即细胞内核酸的积累是这些酶发生突变的结果，并通过激活先天免疫模式识别受体触发炎症反应。
