Indole-3-propionic acid has chemical chaperone activity and suppresses endoplasmic reticulum stress-induced neuronal cell death
Indole-3-propionic acid has chemical chaperone activity and suppresses endoplasmic reticulum stress-induced neuronal cell death
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DOI：
10.1016/j.bbrc.2019.07.074
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发表时间：
2019-10-01
影响因子：
3.1
通讯作者：
Kanzaki, Tetsuto
中科院分区：
文献类型：
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作者：
Mimori, Seisuke;Kawada, Koichi;Kanzaki, Tetsuto
不溶性聚集蛋白通常与神经退行性疾病相关。以前，我们研究了防止变性蛋白质聚集的化学分子伴侣。其中，4-苯基丁酸（4-PBA）具有充分记录的化学伴侣活性，但需要对细胞具有多种作用的剂量，从而阻碍了治疗方案的进一步优化。在这项研究中，我们证明了新化合物吲哚-3-丙酸（IPA）的化学伴侣活性。虽然已经报道IPA可防止β-淀粉样蛋白聚集，但在此我们证明该化合物可抑制变性蛋白的聚集。我们的实验与帕金森氏病的细胞培养模型是第一次表明，IPA防止内质网（ER）的压力，从而防止神经元细胞死亡。我们认为，IPA有可能用于治疗神经退行性疾病和其他疾病，其中ER应激已牵连。(C)2019爱思唯尔公司All rights reserved.
Insoluble aggregated proteins are often associated with neurodegenerative diseases. Previously, we investigated chemical chaperones that prevent the aggregation of denatured proteins. Among these, 4-phenyl butyric acid (4-PBA) has well-documented chemical chaperone activity, but is required at doses that have multiple effects on cells, warranting further optimization of treatment regimens. In this study, we demonstrate chemical chaperone activities of the novel compound indole-3-propionic acid (IPA). Although it has already been reported that IPA prevents beta-amyloid aggregation, herein we show that this compound suppresses aggregation of denatured proteins. Our experiments with a cell culture model of Parkinson's disease are the first to show that IPA prevents endoplasmic reticulum (ER) stress and thereby protects against neuronal cell death. We suggest that IPA has potential for the treatment of neurodegenerative diseases and other diseases for which ER stress has been implicated. (C) 2019 Elsevier Inc. All rights reserved.