One to Rule Them All: A Unique TAU Therapy for Neurodevelopmental Encephalopathies.
One to Rule Them All: A Unique TAU Therapy for Neurodevelopmental Encephalopathies.
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DOI：
10.1177/15357597221126332
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发表时间：
2022-11
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
邵娥，常春伟，李志，于晓霞，何凯，张敏，王晓霞，王志强，刘国强，王志强，于国强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强，刘志强。doi: 10.1126 / scitranslmed。细胞内TAU聚集物的积累是几种神经退行性疾病的标志。然而，TAU的整体遗传减少在其他缺乏TAU病理的脑疾病模型中也是有益的，这表明非聚集TAU的致病作用。在本研究中，在儿童早期严重癫痫性脑病Dravet综合征的小鼠模型中，兴奋性而非抑制性神经元中TAU的条件性消蚀减少了癫痫、癫痫中突然意外死亡、磷酸肌肽3-激酶- akt -雷帕霉素途径的哺乳动物靶点过度激活、脑过度生长（大脑畸形）和自闭症样行为。此外，在出生后第10天开始使用降低tau的反义寡核苷酸治疗，在该小鼠模型中具有类似的治疗效果。我们的研究结果表明，兴奋性神经元是TAU必须减少以抵消与Dravet综合征相关的脑功能障碍的关键细胞类型，并且大脑整体TAU减少可能具有类似的益处，即使是在出生后开始。
TAU Ablation in Excitatory Neurons and Postnatal TAU Knockdown Reduce Epilepsy, SUDEP, and Autism Behaviors in a Dravet Syndrome Model Shao E, Chang C-W, Li Z, Yu X, Ho K, Zhang M, Wang X, Simms J, Lo I, Speckart J, Holtzman J, Yu G-Q, Roberson ED, Mucke L. Sci Transl Med. 2022;14(642):eabm5527. doi:10.1126/scitranslmed.abm5527 Intracellular accumulation of TAU aggregates is a hallmark of several neurodegenerative diseases. However, global genetic reduction of TAU is beneficial also in models of other brain disorders that lack such TAU pathology, suggesting a pathogenic role of nonaggregated TAU. Here, conditional ablation of TAU in excitatory, but not inhibitory, neurons reduced epilepsy, sudden unexpected death in epilepsy, overactivation of the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway, brain overgrowth (megalencephaly), and autism-like behaviors in a mouse model of Dravet syndrome, a severe epileptic encephalopathy of early childhood. Furthermore, treatment with a TAU-lowering antisense oligonucleotide, initiated on postnatal day 10, had similar therapeutic effects in this mouse model. Our findings suggest that excitatory neurons are the critical cell type in which TAU has to be reduced to counteract brain dysfunctions associated with Dravet syndrome and that overall cerebral TAU reduction could have similar benefits, even when initiated postnatally.
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影响因子：
17.1
作者：
通讯作者：
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影响因子：
16.6
作者：
Valassina N;Brusco S;Salamone A;Serra L;Luoni M;Giannelli S;Bido S;Massimino L;Ungaro F;Mazzara PG;D'Adamo P;Lignani G;Broccoli V;Colasante G
通讯作者：
Colasante G
DOI：
10.1523/jneurosci.3191-12.2013
发表时间：
2013-01-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Holth JK;Bomben VC;Reed JG;Inoue T;Younkin L;Younkin SG;Pautler RG;Botas J;Noebels JL
通讯作者：
Noebels JL
影响因子：
5.3
作者：
DeVos, Sarah L.;Goncharoff, Dustin K.;Miller, Timothy M.
通讯作者：
Miller, Timothy M.
tau的减少对兴奋性和抑制神经元的影响不同，降低了兴奋/抑制比，并抵消网络过渡性。
影响因子：
8.8
作者：
Chang CW;Evans MD;Yu X;Yu GQ;Mucke L
通讯作者：
Mucke L