Tau gene alternative splicing: expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases

被引:229
作者
Andreadis, A [1 ]
机构
[1] Univ Massachusetts, Dept Cell Biol, Sch Med, Worcester, MA USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2005年 / 1739卷 / 2-3期
基金
美国国家卫生研究院;
关键词
alternative splicing; MAP tau; neuronal structure and function; neurodegeneration;
D O I
10.1016/j.bbadis.2004.08.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Organization of cytoskeletal elements is critical for cellular migration and maintenance of morphology. Tau protein, which binds to and organizes microtubules, is instrumental in forming and maintaining the neuronal axon. Disturbances in tau expression result in disruption of the neuronal cytoskeleton and formation of pathological tau structures (neurofibrillary tangles, NFTs) found in brains of dementia sufferers. Null tau mice, although viable, exhibit developmental and cognitive defects and transgenic mice which overexpress tau develop severe neuropathies. The neuron-specific tau transcript produces multiple isoforms by intricately regulated alternative splicing. These isoforms modulate tau function in normal brain. Moreover, aberrations in tau splicing regulation directly cause several neurodegenerative diseases. Thus, tau splicing regulation is vital to neuronal health and correct brain function. This review briefly presents our cumulative knowledge of tau splicing-cis elements and trans factors which influence it at the RNA level, its effect on the structure and roles of the tau protein and its repercussions on neuronal morphology and neurodegeneration. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:91 / 103
页数:13
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