Tau exon 10 alternative splicing and tauopathies.
Tau exon 10 alternative splicing and tauopathies.
复制标题
tau外显子10替代剪接和tauopathies。
DOI：
10.1186/1750-1326-3-8
复制
发表时间：
2008-07-10
影响因子：
15.1
通讯作者：
Gong, Cheng-Xin
中科院分区：
文献类型：
--
作者：
Liu, Fei;Gong, Cheng-Xin
微管相关蛋白tau蛋白的缺失在几种神经退行性疾病中的神经退行性变中起核心作用，这些神经退行性疾病统称为tau蛋白病。tau蛋白的六种亚型在成年人脑中表达，其由单个tau基因产生的前mRNA的选择性剪接产生。tau外显子10的选择性剪接导致含有三个或四个微管结合重复序列（分别为3R-tau和4 R-tau）的tau同种型。在正常成人脑中表达大约相等水平的3R-tau和4 R-tau，但在几种tau蛋白病中脑中3R-tau/4 R-tau比率改变。在一些患有与17号染色体连锁的帕金森综合征（FTDP-17）的额颞叶痴呆（frontotemporal dementia with Parkinsonism）的个体中发现tau基因的沉默突变和内含子突变，其仅破坏tau外显子10剪接，但不改变tau的一级序列，这表明tau外显子10选择性剪接以及因此的3R-tau/4 R-tau平衡的失调足以引起神经变性和痴呆。在这里，我们回顾了tau的基因结构、转录本和蛋白亚型，然后是决定3R-tau或4 R-tau表达的第10号外显子剪接的调节。最后，在几个tau蛋白病的外显子10剪接失调进行了讨论。了解tau外显子10剪接的分子机制以及它在tau蛋白病中是如何被破坏的，将为这些tau蛋白病的机制提供新的见解，并有助于确定治疗这些疾病的新的治疗靶点。
Abnormalities of microtubule-associated protein tau play a central role in neurofibrillary degeneration in several neurodegenerative disorders that collectively called tauopathies. Six isoforms of tau are expressed in adult human brain, which result from alternative splicing of pre-mRNA generated from a single tau gene. Alternative splicing of tau exon 10 results in tau isoforms containing either three or four microtubule-binding repeats (3R-tau and 4R-tau, respectively). Approximately equal levels of 3R-tau and 4R-tau are expressed in normal adult human brain, but the 3R-tau/4R-tau ratio is altered in the brains in several tauopathies. Discovery of silence mutations and intronic mutations of tau gene in some individuals with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), which only disrupt tau exon 10 splicing but do not alter tau's primary sequence, demonstrates that dysregulation of tau exon 10 alternative splicing and consequently of 3R-tau/4R-tau balance is sufficient to cause neurodegeneration and dementia. Here, we review the gene structure, transcripts and protein isoforms of tau, followed by the regulation of exon 10 splicing that determines the expression of 3R-tau or 4R-tau. Finally, dysregulation of exon 10 splicing of tau in several tauopathies is discussed. Understanding the molecular mechanisms by which tau exon 10 splicing is regulated and how it is disrupted in tauopathies will provide new insight into the mechanisms of these tauopathies and help identify new therapeutic targets to treat these disorders.
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影响因子：
11.4
作者：
EPERON, IC;IRELAND, DC;KRAINER, AR
通讯作者：
KRAINER, AR
影响因子：
11.4
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
11.4
作者：
GOEDERT, M;JAKES, R
通讯作者：
JAKES, R
影响因子：
14.5
作者：
Bronner, IF;ter Meulen, BC;van Swieten, JC
通讯作者：
van Swieten, JC