激活蛋白酶体以预防蛋白毒性
Priming the Proteasome to Protect against Proteotoxicity.
机构信息
University of South Dakota Sanford School of Medicine, Vermillion, SD 57069, USA.
University of South Dakota Sanford School of Medicine, Vermillion, SD 57069, USA.
出版信息
Trends Mol Med. 2020 Jul;26(7):639-648. doi: 10.1016/j.molmed.2020.02.007. Epub 2020 Mar 26.
Abstract
Increased proteotoxic stress (IPTS) resulting from the increased production or decreased removal of abnormally folded proteins is recognized as an important pathogenic factor for a large group of highly disabling and life-threatening human diseases, such as neurodegenerative disorders and many heart diseases. The proteasome is pivotal to the timely removal of abnormal proteins but its functional capacity often becomes inadequate in the disease conditions; consequently, proteasome functional insufficiency in return exacerbates IPTS. Recent research in proteasome biology reveals that the proteasome can be activated by endogenous protein kinases, making it possible to pharmacologically prime the proteasome for treating diseases with IPTS.
摘要
蛋白质毒性应激（IPTS）增加，这是由于异常折叠蛋白的产生增加或清除减少所致，被认为是一大类高度致残和危及生命的人类疾病（如神经退行性疾病和许多心脏病）的重要致病因素。蛋白酶体对于及时清除异常蛋白至关重要，但在疾病情况下其功能能力往往不足；因此，蛋白酶体功能不足反过来又会加剧 IPTS。蛋白酶体生物学的最新研究表明，蛋白酶体可以被内源性蛋白激酶激活，这使得用蛋白酶体治疗 IPTS 疾病的药物有了可能。
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