Glucocerebrosidase as a therapeutic target for Parkinson's disease

Chen Yu; Sam Richard; Sharma PankajChen LuDo JennySidransky Ellen

首页> 外文期刊>Expert opinion on therapeutic targets >Glucocerebrosidase as a therapeutic target for Parkinson's disease

【24h】

Glucocerebrosidase as a therapeutic target for Parkinson's disease

机译：Glucocerebrosidase as a therapeutic target for Parkinson's disease

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Introduction: The association between Gaucher disease, caused by the inherited deficiency of glucocerebrosidase, and Parkinson's disease was first recognized in the clinic, noting that patients with Gaucher disease and their carrier relatives had an increased incidence of Parkinson's disease. Currently, mutations in glucocerebrosidase (GBA1) are the most common genetic risk factor for Parkinson's disease and dementia with Lewy bodies, with an inverse relationship between glucocerebrosidase and alpha-synuclein, a key factor in Parkinson pathogenesis. The hypothesis that therapeutic enhancement of brain glucocerebrosidase levels might reduce the aggregation, accumulation or spread of alpha-synuclein has spurred great interest in glucocerebrosidase as a novel therapeutic target. Area covered: This article explores the potential molecular mechanisms underlying the association between GBA1 mutations and Parkinson's disease and outlines therapeutic strategies to increase brain glucocerebrosidase, including gene therapy, targeted delivery of recombinant glucocerebrosidase to the brain, small-molecule chaperones to rescue mutant glucocerebrosidase, and small-molecule modulators to activate wild-type glucocerebrosidase. Expert opinion: Although an improved understanding of the mechanistic basis for GBA1-associated parkinsonism is essential, enhancing levels of brain glucocerebrosidase may have wide therapeutic implications. While gene therapy may ultimately be effective, less expensive and invasive small-molecule non-inhibitory chaperones or activators could significantly impact the disease course.

著录项

来源
《Expert opinion on therapeutic targets》 |2020年第6期|287-294|共8页
作者
Chen Yu; Sam Richard; Sharma PankajChen LuDo JennySidransky Ellen;
展开▼
作者单位

NHGRI, Med Genet Branch, NIH, Bldg 35A,Room 1E623,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA;

NIH, Natl Ctr Advancing Translat Sci, Rockville, MD USA;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类药学;
关键词
Parkinson's disease; gaucher disease; alpha-synuclein; glucocerebrosidase; lysosome; chaperones; gene therapy;

Glucocerebrosidase as a therapeutic target for Parkinson's disease

摘要

著录项

相关主题

期刊订阅