The Unfolded Protein Response Protects from Tau Neurotoxicity In Vivo

被引:72
作者
Loewen, Carin A. [1 ]
Feany, Mel B. [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
ENDOPLASMIC-RETICULUM STRESS; CELL-CYCLE REENTRY; ALZHEIMERS-DISEASE; RETINAL DEGENERATION; NEUROFIBRILLARY TANGLES; DROSOPHILA; NEURODEGENERATION; PHOSPHORYLATION; TAUOPATHY; TOXICITY;
D O I
10.1371/journal.pone.0013084
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
The unfolded protein response is a critical system by which the cell handles excess misfolded protein in the secretory pathway. The role of the system in modulating the effects of aggregation prone cytosolic proteins has received less attention. We use genetic reporters to demonstrate activation of the unfolded protein response in a transgenic Drosophila model of Alzheimer's disease and related tauopathies. We then use loss of function genetic reagents to support a role for the unfolded protein response in protecting from tau neurotoxicity. Our findings suggest that the unfolded protein response can ameliorate the toxicity of tau in vivo.
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页数:6
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