期刊
ACS CHEMICAL NEUROSCIENCE
卷 10, 期 9, 页码 3969-3985出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.9b00167
关键词
arginine; arginine ethyl ester; polyglutamine; Huntington's disease; aggregation
资金
- IIT Kanpur
- ICMR
- Indian Council of Medical Research, Government of India [ICMR/BSBE/2016489]
- Indian Institute of Technology [IITK/BSBE/20100293]
- DBT
- CSIR
Huntington's disease (HD) is a genetic disorder caused by a CAG expansion mutation in the huntingtin gene leading to polyglutamine (polyQ) expansion in the N-terminal part of huntingtin (Httex1). Expanded polyQ through a complex aggregation pathway, forms aggregates in neurons and presents a potential therapeutic target. Here we show Httex1 aggregation suppression by arginine and arginine ethyl ester (AEE) in vitro, as well as in yeast and mammalian cell models of HD, bearing expanded polyQ These molecules also rescue locomotion dysfunction in HD Drosophila model. Both molecules alter the hydrogen bonding network of polyQ to enhance its aqueous solubility and delay aggregation. AEE shows direct binding with the NT17 part of Httex1 to induce structural changes to impart an enhanced inhibitory effect. This study provides a platform for the development of better arginine based therapeutic molecules against polygrich Httexl aggregation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据