{"title":"Neurodegenerative diseases associated with the disruption of proteostasis and their therapeutic strategies using chemical chaperones.","authors":"Takashi Sugiyama, Hideki Nishitoh","doi":"10.1093/jb/mvae048","DOIUrl":null,"url":null,"abstract":"<p><p>Aberrant proteostasis is thought to be involved in the pathogenesis of neurodegenerative diseases. Some proteostasis abnormalities are ameliorated by chaperones. Chaperones are divided into three groups: molecular, pharmacological and chemical. Chemical chaperones intended to alleviate stress in organelles, such as the endoplasmic reticulum (ER), are now being administered clinically. Of the chemical chaperones, 4-phenylbutyrate (4-PBA) has been used as a research reagent, and its mechanism of action includes chaperone effects and the inhibition of histone deacetylase. Moreover, it also binds to the B-site of SEC24 and regulates COPII-mediated transport from the ER. Although its therapeutic effect may not be strong, elucidating the mechanism of action of 4-PBA may contribute to the identification of novel therapeutic targets for neurodegenerative diseases.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"179-186"},"PeriodicalIF":2.1000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/jb/mvae048","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aberrant proteostasis is thought to be involved in the pathogenesis of neurodegenerative diseases. Some proteostasis abnormalities are ameliorated by chaperones. Chaperones are divided into three groups: molecular, pharmacological and chemical. Chemical chaperones intended to alleviate stress in organelles, such as the endoplasmic reticulum (ER), are now being administered clinically. Of the chemical chaperones, 4-phenylbutyrate (4-PBA) has been used as a research reagent, and its mechanism of action includes chaperone effects and the inhibition of histone deacetylase. Moreover, it also binds to the B-site of SEC24 and regulates COPII-mediated transport from the ER. Although its therapeutic effect may not be strong, elucidating the mechanism of action of 4-PBA may contribute to the identification of novel therapeutic targets for neurodegenerative diseases.
蛋白稳态异常被认为与神经退行性疾病的发病机制有关。一些蛋白稳态异常可通过伴侣素得到改善。伴侣分为三类：分子伴侣、药理学伴侣和化学伴侣。化学伴侣旨在减轻细胞器（如内质网）的压力，目前已在临床上使用。在化学伴侣剂中，4-苯基丁酸酯（4-PBA）已被用作研究试剂，其作用机制包括伴侣效应和抑制组蛋白去乙酰化酶。此外，它还能与 SEC24 的 B 位点结合，调节 COPII 介导的从 ER 的转运。虽然 4-PBA 的治疗效果可能不强，但阐明其作用机制可能有助于确定神经退行性疾病的新治疗靶点。
期刊介绍：
The Journal of Biochemistry founded in 1922 publishes the results of original research in the fields of Biochemistry, Molecular Biology, Cell, and Biotechnology written in English in the form of Regular Papers or Rapid Communications. A Rapid Communication is not a preliminary note, but it is, though brief, a complete and final publication. The materials described in Rapid Communications should not be included in a later paper. The Journal also publishes short reviews (JB Review) and papers solicited by the Editorial Board.
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