Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells.
Cycloheximide Treatment Causes a ZVAD-Sensitive Protease-Dependent Cleavage of Human Tau in Drosophila Cells.
复制标题
放线菌酮处理导致果蝇细胞中 ZVAD 敏感的蛋白酶依赖性人 Tau 蛋白裂解
DOI：
10.3233/jad-150423
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Dou F
中科院分区：
文献类型：
--
作者：
Geng J;Xia L;Li W;Zhao C;Dou F
神经原纤维缠结是阿尔茨海默病的主要病理特征。不溶性tau蛋白是神经原纤维缠结的主要成分。神经元中tau蛋白降解途径的缺陷可能导致tau蛋白的积聚和随后的聚集。目前，不同的研究小组对tau降解途径的研究结果相互矛盾。这种差异很可能是由于这些研究中使用的不同细胞系和方法造成的。在这项研究中，我们发现放线菌亚胺处理诱导了果蝇KC细胞中对zVAD敏感的蛋白酶的温和激活，导致其C末端tau的裂解；这种裂解可能会产生误导性的tau蛋白降解模式，这取决于在检测中使用的抗体。由于放线菌亚胺是一种广泛用于研究蛋白质降解的化学试剂，我们在这里观察到的意想不到的人工效应表明，放线菌亚胺不适合于研究tau的降解。其他方法，如诱导表达系统和脉冲追逐试验，可能更适合于研究生理条件下tau的降解。
Neurofibrillary tangles are the main pathological feature of Alzheimer’s disease. Insoluble tau protein is the major component of neurofibrillary tangles. Defects in the tau protein degradation pathway in neurons can lead to the accumulation of tau and its subsequent aggregation. Currently, contradictory results on the tau degradation pathway have been reported by different groups. This discrepancy is most likely due to different cell lines and methods used in those studies. In this study, we found that cycloheximide treatment induced mild activation of a ZVAD-sensitive protease in Drosophila Kc cells, resulting in cleavage of tau at its C-terminus; this cleavage could generate misleading tau protein degradation pattern results depending on the antibodies used in the assay. Because cycloheximide is a broadly used chemical reagent for the study of protein degradation, the unexpected artificial effect we observed here indicates that cycloheximide is not suitable for the study of tau degradation. Other methods, such as inducible expression systems and pulse-chase assays, may be more appropriate for studying tau degradation under physiological conditions.