A cell-based screen for drugs to treat Huntington's disease

被引：108

作者：

Aiken, CT

Tobin, AJ

Schweitzer, ES

机构：

[1] Univ Calif Los Angeles, Inst Brain Res, Dept Physiol Sci, Gonda Goldschmied Neurosci & Genet Res Ctr, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Inst Brain Res, Dept Neurol, Los Angeles, CA 90095 USA

来源：

NEUROBIOLOGY OF DISEASE | 2004年 / 16卷 / 03期

关键词：

drug screen; Huntington's disease; PC12; cells; LDH assay;

D O I：

10.1016/j.nbd.2004.04.001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We have developed a medium-throughput cell-based assay to screen drugs for Huntington's disease (HD). The assay measures the ability of drugs to protect cultured neuronal (PC12) cells from death caused by an expanded polyglutamine (poly Q) form of huntingtin exon 1. Using this assay, we have blindly screened a library of 1040 compounds compiled by the NINDS: the NIH Custom Collection (NCC). Each compound was tested at five concentrations for its ability to protect cells against huntingtin-induced cell death as well as for its toxicity. Of the compounds tested, 18 prevented cell death completely, and 51 partially. Some of these also exhibited toxicity at higher doses. The majority of drugs (81%) were ineffective. Caspase inhibitors and cannabinoids showed reproducible protection in our assay. We believe these compounds, and others in our hit list, are appealing candidates for further investigation. Additionally, this assay is amenable to scaling up to screen additional compounds for treating Huntington's disease. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：546 / 555

页数：10

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