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

Biochemical and Biophysical Research Communications
Seisuke MimoriTetsuto Kanzaki

Abstract

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.

References

Mar 3, 2004·Annals of Neurology·Tetsuro MurakamiKoji Abe
Jan 10, 2012·Biological & Pharmaceutical Bulletin·Seisuke MimoriHiroshi Hamana
Jan 18, 2015·Bioorganic & Medicinal Chemistry Letters·Seisuke MimoriHiroshi Hamana
Feb 11, 2015·The International Journal of Biochemistry & Cell Biology·P S KolbK Ask
Feb 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ozlem TufanliEbru Erbay
Mar 13, 2017·Biochemical and Biophysical Research Communications·Chandak UpaguptaJeffrey G Dickhout
Jun 13, 2017·Experimental Physiology·Colin N Young
Mar 1, 2019·Nature Communications·Takayoshi SasakoKohjiro Ueki

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Citations

May 19, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Dustin M LeeChristopher L Gentile
Jan 16, 2021·International Journal of Tryptophan Research : IJTR·Michelle L GarcezGilles J Guillemin
Feb 16, 2021·Frontiers in Physiology·Alessandro EvangelistiFederica Del Monte
Dec 9, 2020·International Journal of Molecular Sciences·Olga V AverinaVladimir P Chekhonin
Aug 18, 2021·The International Journal of Neuroscience·Rimaljot SinghTanzeer Kaur
Sep 29, 2021·Journal of Biochemical and Molecular Toxicology·Rahagir SalekeenKazi Mohammed Didarul Islam

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