The pathogenesis of neurodegenerative diseases such as Alzheimer＇s and Parkinson＇s diseases involves the aggregation of denatured and misfolded nascent proteins. Consequently, many pharmacological approaches have be...The pathogenesis of neurodegenerative diseases such as Alzheimer＇s and Parkinson＇s diseases involves the aggregation of denatured and misfolded nascent proteins. Consequently, many pharmacological approaches have been developed to prevent protein aggregation. 4-Phenylbutyric acid （4-PBA） is a chemical chaperone that shows potential as a candidate drug for the treatment of neurodegenerative diseases. The main actions of chemical chaperones are the amelioration of unfolded proteins and the suppression of their aggregation, which result in protective effects against endoplasmic reticulum stress-induced neuronal cell death. Furthermore, 4-PBA exhibits inhibitory activity against histone deacetylases （HDACs）. However, owing to the problematically high doses of 4-PBA currently required for therapeutic efficacy, the optimization of 4-PBA is crucial for its effective medicinal application. In the present review, we summarize the recent advances in research on the basic actions of 4-PBA and its derivatives. We also discuss whether these compounds could be viable therapeutic agents against neurodegenerative diseases.展开更多
The sigma receptor (Sig-R) was first reported by Martin et al.(1976) and was initially classified into the opioid receptor family. However, Sig-R was subsequently found to differ from the opioid receptor in various st...The sigma receptor (Sig-R) was first reported by Martin et al.(1976) and was initially classified into the opioid receptor family. However, Sig-R was subsequently found to differ from the opioid receptor in various studies including ligand binding assays and autoradiography analysis (Tam and Cook, 1984). Sig-R is widely distributed in tissues such as central nervous, digestive, immune, and endocrine tissues. There are two types of Sig-R: sigma-1 (Sig-1R) and sigma-2 receptors (Sig-2R).展开更多
文摘The pathogenesis of neurodegenerative diseases such as Alzheimer＇s and Parkinson＇s diseases involves the aggregation of denatured and misfolded nascent proteins. Consequently, many pharmacological approaches have been developed to prevent protein aggregation. 4-Phenylbutyric acid （4-PBA） is a chemical chaperone that shows potential as a candidate drug for the treatment of neurodegenerative diseases. The main actions of chemical chaperones are the amelioration of unfolded proteins and the suppression of their aggregation, which result in protective effects against endoplasmic reticulum stress-induced neuronal cell death. Furthermore, 4-PBA exhibits inhibitory activity against histone deacetylases （HDACs）. However, owing to the problematically high doses of 4-PBA currently required for therapeutic efficacy, the optimization of 4-PBA is crucial for its effective medicinal application. In the present review, we summarize the recent advances in research on the basic actions of 4-PBA and its derivatives. We also discuss whether these compounds could be viable therapeutic agents against neurodegenerative diseases.
基金supported by Japan Society for the Promotion of Science KAKENHI(JP16K18888,to KT)
文摘The sigma receptor (Sig-R) was first reported by Martin et al.(1976) and was initially classified into the opioid receptor family. However, Sig-R was subsequently found to differ from the opioid receptor in various studies including ligand binding assays and autoradiography analysis (Tam and Cook, 1984). Sig-R is widely distributed in tissues such as central nervous, digestive, immune, and endocrine tissues. There are two types of Sig-R: sigma-1 (Sig-1R) and sigma-2 receptors (Sig-2R).
