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Neuroprotective Effects of 4-phenylbutyric Acid and Its Derivatives： Possible Therapeutics for Neurodegenerative Diseases

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Journal of Health Science 2017年第1期5卷 9-17页

作者： seisuke mimori Toru Hosoi Masayuki Kaneko Koichiro Ozawa Tetsuto Kanzaki Akinori Nishi Yasuyuki Nomura Department of Clinical Medicine Chiba Institute of Science Choshi 288-0025 Japan Department of Pharmacotherapy Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima734-8553 Japan Department of Biochemistry Institute of Biomedical & Health Sciences Hiroshima University Hiroshima 734-8553 Japan Department of Drug Informatics Graduate School and Faculty of Pharmaceutical Sciences Chiba University Chiba 260-8675Japan Department of Pharmacology Kurume University School of Medicine Kurume 830-0011 Japan

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.

关键词： 4-Phenylbutyric acid (4-PBA) neurodegenerative diseases chemical chaperone histone deacetylase (HDAC).

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