Suppressive effects of 4‐phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress

@article{Kubota2006SuppressiveEO,
  title={Suppressive effects of 4‐phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress},
  author={Kyoko Kubota and Yoshifumi Niinuma and Masayuki Kaneko and Yasunobu Okuma and Mami Sugai and Tomohiro Omura and Mai Uesugi and Takashi Uehara and Toru Hosoi and Yasuyuki Nomura},
  journal={Journal of Neurochemistry},
  year={2006},
  volume={97}
}
Endoplasmic reticulum (ER) stress is defined as an accumulation of unfolded proteins in the endoplasmic reticulum. 4‐phenylbutyrate (4‐PBA) has been demonstrated to promote the normal trafficking of the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) mutant from the ER to the plasma membrane and to restore activity. We have reported that 4‐PBA protected against cerebral ischemic injury and ER stress‐induced neuronal cell death. In this study, we revealed that 4‐PBA possesses… 
Protective effects of 4-phenylbutyrate derivatives on the neuronal cell death and endoplasmic reticulum stress.
TLDR
3-PPA and 4-PBA significantly suppressed neuronal cell death caused by ER stress induced by the overexpression of Pael-R, and suggest that terminal aromatic substituted fatty acids are potential candidates for the treatment of neurodegenerative diseases.
Induction of macroautophagy by overexpression of the Parkinson's disease‐associated GPR37 receptor
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Findings show that G PR37 overexpression per se can induce cellular autophagy, which may prevent the selective degeneration of GPR37‐expressing neurons, as reported for Parkinson's and related neurodegenerative diseases.
The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis.
Proteomic profile of 4-PBA treated human neuronal cells during ER stress.
TLDR
It is posited here that 4-PBA acts as an authentic chemical chaperone by aiding protein folding in the ER by alleviating both the toxicity and proteomic alterations, induced by an ER stress inducer.
The chemical chaperone 4-phenylbutyrate inhibits adipogenesis by modulating the unfolded protein response[S]
TLDR
It is suggested that UPR activation contributes to adipogenesis and that blocking its activation with 4-PBA prevents adipocyte differentiation and weight gain in mice.
4-Phenylbutyrate suppresses the unfolded protein response without restoring protein folding in Saccharomyces cerevisiae
TLDR
Observations indicate that at least in the case of yeast cells, 4-PBA suppresses the UPR not through restoration of the ER function to correctly fold proteins, but through the accelerated degradation of Ire1.
4‐Phenylbutyrate restores the functionality of a misfolded mutant low‐density lipoprotein receptor
TLDR
The data suggest that rescue of mutant low‐density lipoprotein receptor is possible and that it might be feasible to develop pharmacologic chaperones to treat familial hypercholesterolemia patients with class’2 mutations.
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