在一种神经退行性小鼠模型中抑制tau蛋白可改善记忆功能。
Tau suppression in a neurodegenerative mouse model improves memory function.
作者信息
Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe K H
机构信息
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
出版信息
Science. 2005 Jul 15;309(5733):476-81. doi: 10.1126/science.1113694.
Abstract
Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.
摘要
神经原纤维缠结（NFTs）是神经退行性疾病患者大脑中最常见的神经元内包涵体，并被认为介导神经元死亡和认知缺陷。在此，我们发现表达可抑制的人类tau变异体的小鼠出现了与年龄相关的进行性NFTs、神经元丢失和行为障碍。在转基因tau被抑制后，记忆功能恢复，神经元数量稳定，但令我们惊讶的是，NFTs继续积累。因此，在这种tau蛋白病模型中，NFTs不足以导致认知衰退或神经元死亡。
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本文引用的文献
1
Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death.
Nature. 2004 Oct 14;431(7010):805-10. doi: 10.1038/nature02998.
2
Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome.
Neuron. 2004 Aug 5;43(3):321-32. doi: 10.1016/j.neuron.2004.07.003.
3
Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function.
Arch Neurol. 2004 Mar;61(3):378-84. doi: 10.1001/archneur.61.3.378.
4
Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms.
J Neurochem. 2003 Aug;86(3):582-90. doi: 10.1046/j.1471-4159.2003.01879.x.
5
Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment.
Arch Neurol. 2003 May;60(5):729-36. doi: 10.1001/archneur.60.5.729.
6
Tau filament formation and associative memory deficit in aged mice expressing mutant (R406W) human tau.
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13896-901. doi: 10.1073/pnas.202205599. Epub 2002 Oct 4.
7
The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease.
J Neurosci. 2002 Mar 1;22(5):1858-67. doi: 10.1523/JNEUROSCI.22-05-01858.2002.
8
Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils.
Science. 2001 Aug 24;293(5534):1491-5. doi: 10.1126/science.1062097.
9
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP.
Science. 2001 Aug 24;293(5534):1487-91. doi: 10.1126/science.1058189.
10
A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease.
Nature. 2000;408(6815):975-9. doi: 10.1038/35050103.
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