TDP-43 in aging and Alzheimer's disease - a review.
TDP-43 in aging and Alzheimer's disease - a review.
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发表时间：
2011-01
影响因子：
1.4
通讯作者：
Andrea C. Wilson;B. Dugger;D. Dickson;Deng-shun Wang
中科院分区：
文献类型：
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作者：
Andrea C. Wilson;B. Dugger;D. Dickson;Deng-shun Wang
TDP-43（Transactive response DNA-binding protein of 43 kDa）是一种RNA和DNA结合蛋白，在应激反应中参与转录抑制、RNA剪接和RNA代谢，是肌萎缩侧索硬化症（ALS）和额颞叶变性伴泛素包涵体的神经元包涵体的主要成分，现称为FTLD-TDP。虽然最初认为TDP-43病理学相对特异于ALS和FTLD-TDP，但现在已经在许多其他神经退行性疾病中检测到TDP-43病理学，许多与tau病理学相关，包括关岛帕金森痴呆综合征和阿尔茨海默病（AD）。在25%至50%的AD病例中检测到TDP-43病理学，尤其是具有更严重临床表型和更大阿尔茨海默型病理学的那些，以及具有海马硬化（HS）的AD病例。HS的特征在于影响海马CA 1区的选择性神经元损失，并且大多数HS病例（伴或不伴AD）具有TDP-43病理学。TDP-43病理学是否仅仅是AD中的偶然发现或实际上导致更严重的临床表型仍未解决。TDP-43在AD风险增加的正常老年人中的存在将加强这不仅仅是终末期AD中的次要或偶然发现的论点。有限的研究表明，TDP-43病理在神经系统正常的老年人中不常见（3%或更少）。我们提供了一个概述什么是已知的TDP-43在AD，正常老化和其他疾病，并建议TDP-43蛋白质病被认为是两个类-主要和次要的。
Transactive response DNA-binding protein of 43 kDa (TDP-43), an RNA and DNA binding protein involved in transcriptional repression, RNA splicing and RNA metabolism during the stress response, is the major component of neuronal inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions, now referred to as FTLD-TDP. While initially thought to be relatively specific to ALS and FTLD-TDP, TDP-43 pathology has now been detected in a number of other neurodegenerative diseases, many associated with tau pathology, including Guam Parkinson dementia complex and Alzheimer's disease (AD). TDP-43 pathology is detected in 25% to 50% of AD cases, especially those with more severe clinical phenotype and greater Alzheimer type pathology, as well as AD cases with hippocampal sclerosis (HS). HS is characterized by selective neuronal loss affecting CA1 sector of the hippocampus, and most cases of HS, with or without AD, have TDP-43 pathology. Whether TDP-43 pathology is merely an incidental finding in AD or actually contributing to the more severe clinical phenotype remains unresolved. Presence of TDP-43 in normal elderly, who are at increased risk for AD, would strengthen the argument that it is not merely a secondary or incidental finding in end stage AD. Limited studies suggest that TDP-43 pathology is infrequent in neurologically normal elderly (3% or less). We provide an overview of what is known about TDP-43 in AD, normal aging and in other disorders and suggest that TDP-43 proteinopathies be considered in two classes - primary and secondary.