Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington's and Parkinson's diseases

被引：203

作者：

Bodner, RA

Outeiro, TF

Altmann, S

Maxwell, MM

Cho, SH

Hyman, BT

McLean, PJ

Young, AB

Housman, DE

Kazantsev, AG

机构：

[1] MIT, Ctr Canc Res, Cambridge, MA 02139 USA

[2] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA

[3] Harvard Univ, Sch Med, Boston, MA 02129 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2006年 / 103卷 / 11期

关键词：

misfolded proteins; neuroclegenerative disease;

D O I：

10.1073/pnas.0511256103

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Misfolded proteins accumulate in many neurodegenerative diseases, including huntingtin in Huntington's disease and alpha-synuclein in Parkinson's disease. The disease-causing proteins can take various conformations and are prone to aggregate and form larger cytoplasmic or nuclear inclusions. One approach to the development of therapeutic intervention for these diseases has been to identify chemical compounds that reduce the size or number of inclusions. We have, however, identified a compound that promotes inclusion formation in cellular models of both Huntington's disease and Parkinson's disease. Of particular interest, this compound prevents huntingtin-mediated proteasome dysfunction and reduces a-synuclein-mediated toxicity. These results demonstrate that compounds that increase inclusion formation may actually lessen cellular pathology in both Huntington's and Parkinson's diseases, suggesting a therapeutic approach for neurodegenerative diseases caused by protein misfolding.

引用

收藏

页码：4246 / 4251

页数：6

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