稳态与超越：ATF6 在缺血性疾病中的作用。
Proteostasis and Beyond: ATF6 in Ischemic Disease.
机构信息
San Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA 92182, USA.
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
Trends Mol Med. 2019 Jun;25(6):538-550. doi: 10.1016/j.molmed.2019.03.005. Epub 2019 May 8.
Abstract
Endoplasmic reticulum (ER) stress is a pathological hallmark of numerous ischemic diseases, including stroke and myocardial infarction (MI). In these diseases, ER stress leads to activation of the unfolded protein response (UPR) and subsequent adaptation of cellular physiology in ways that dictate cellular fate following ischemia. Recent evidence highlights a protective role for the activating transcription factor 6 (ATF6) arm of the UPR in mitigating adverse outcomes associated with ischemia/reperfusion (I/R) injury in multiple disease models. This suggests ATF6 as a potential therapeutic target for intervening in diverse ischemia-related disorders. Here, we discuss the evidence demonstrating the importance of ATF6 signaling in protecting different tissues against ischemic damage and discuss preclinical results focused on defining the potential for pharmacologically targeting ATF6 to intervene in such diseases.
摘要
内质网（ER）应激是许多缺血性疾病的病理标志，包括中风和心肌梗死（MI）。在这些疾病中，ER 应激会导致未折叠蛋白反应（UPR）的激活，随后细胞生理学以决定缺血后细胞命运的方式适应。最近的证据强调了 UPR 的激活转录因子 6（ATF6）臂在减轻多种疾病模型中与缺血/再灌注（I/R）损伤相关的不良后果中的保护作用。这表明 ATF6 是干预多种与缺血相关疾病的潜在治疗靶点。在这里，我们讨论了证明 ATF6 信号在保护不同组织免受缺血性损伤中的重要性的证据，并讨论了专注于确定药理学靶向 ATF6 以干预此类疾病的潜力的临床前结果。
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