%0 Journal Article
%T Neurodegenerative diseases associated with the disruption of proteostasis and their therapeutic strategies using chemical chaperones.
%A Sugiyama T
%A Nishitoh H
%J J Biochem
%V 0
%N 0
%D 2024 Jul 2
%M 38955196
%F 3.241
%R 10.1093/jb/mvae048
%X 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.