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

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...

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Published inBiochemical 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
LanguageEnglish
Published United States Elsevier Inc 01.10.2019
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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. •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.
AbstractList 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.
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.
Author Takahashi, Masato
Mizoi, Kenta
Okuma, Yasunobu
Kanzaki, Tetsuto
Mimori, Seisuke
Hosokawa, Masakiyo
Kawada, Koichi
Saito, Ryo
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/31378367$$D View this record in MEDLINE/PubMed
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Issue 4
Keywords 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
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Snippet Insoluble aggregated proteins are often associated with neurodegenerative diseases. Previously, we investigated chemical chaperones that prevent the...
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SubjectTerms 4-Phenyl butyric acid
Chemical chaperone
Endoplasmic reticulum stress
Indole-3-propionic acid
Parkinson's disease
Title Indole-3-propionic acid has chemical chaperone activity and suppresses endoplasmic reticulum stress-induced neuronal cell death
URI https://dx.doi.org/10.1016/j.bbrc.2019.07.074
https://www.ncbi.nlm.nih.gov/pubmed/31378367
https://search.proquest.com/docview/2268575373
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