Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration

被引：517

作者：

Lee, Edward B. ^{[2
]}

Lee, Virginia M-Y ^{[1
]}

Trojanowski, John Q. ^{[1
]}

机构：

[1] Univ Penn, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Inst Aging, Philadelphia, PA 19104 USA

[2] Univ Penn, Translat Neuropathol Res Lab, Dept Pathol & Lab Med, Div Neuropathol, Philadelphia, PA 19104 USA

来源：

NATURE REVIEWS NEUROSCIENCE | 2012年 / 13卷 / 01期

基金：

美国国家卫生研究院;

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; DNA-BINDING PROTEIN; AMYLOID PRECURSOR PROTEIN; NUCLEAR FACTOR TDP-43; MOTOR-NEURON DISEASE; C-TERMINAL FRAGMENTS; TRANSGENIC MICE; ALZHEIMERS-DISEASE; DROSOPHILA MODEL;

D O I：

10.1038/nrn3121

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

RNA-binding proteins, and in particular TAR DNA-binding protein 43 (TDP43), are central to the pathogenesis of motor neuron diseases and related neurodegenerative disorders. Studies on human tissue have implicated several possible mechanisms of disease and experimental studies are now attempting to determine whether TDP43-mediated neurodegeneration results from a gain or a loss of function of the protein. In addition, the distinct possibility of pleotropic or combined effects - in which gains of toxic properties and losses of normal TDP43 functions act together - needs to be considered.

引用

页码：38 / 50

页数：13

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