Indole-3-propionic acid has chemical chaperone activity and suppresses endoplasmic reticulum stress-induced neuronal cell death

• Published in: Biochemical and biophysical research communications Vol. 517; no. 4; pp. 623 - 628
• Main Authors: Mimori, Seisuke, Kawada, Koichi, Saito, Ryo, Takahashi, Masato, Mizoi, Kenta, Okuma, Yasunobu, Hosokawa, Masakiyo, Kanzaki, Tetsuto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: 4-Phenyl butyric acid; Chemical chaperone; Endoplasmic reticulum stress; Indole-3-propionic acid; Parkinson's disease; Chemical chaperone; Parkinson's disease; SDS; GRP; 4-Phenyl butyric acid; ER; Endoplasmic reticulum stress; BSA; DMEM; CV; Pael-R; Indole-3-propionic acid; IPA; GAPDH; HDAC
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.07.074

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 β-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. •IPA is the new chemical chaperone with equal or better efficacy than 4-PBA.•IPA suppresses denatured protein aggregation in vitro.•IPA suppresses the ER stress-induced neuronal cell death.•IPA suppressed oxidative stress-induced neuronal cell death in a PD model.•Contribution of IPA to HDAC inhibition during cell death suppression was evaluated.