TDP-43 Pathology in Alzheimer's Disease.
TDP-43 Pathology in Alzheimer's Disease.
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DOI：
10.1186/s13024-021-00503-x
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发表时间：
2021-12-20
影响因子：
15.1
通讯作者：
Zhao N
中科院分区：
文献类型：
--
作者：
Meneses A;Koga S;O'Leary J;Dickson DW;Bu G;Zhao N
43 kDa的反式反应DNA结合蛋白（TDP-43）是由TARDBP基因编码的核内蛋白，其参与RNA剪接、运输、稳定，并因此参与基因表达的调节。含有磷酸化和截短形式的TDP-43的细胞质包涵体是肌萎缩侧索硬化症（ALS）和额颞叶变性（FTLD）的一个子集的标志。此外，在高达57%的阿尔茨海默病（AD）病例中发现了TDP-43包涵体，最常见的是边缘分布，伴或不伴海马硬化。在某些情况下，TDP-43沉积物也发现在神经元缠结的神经元。与没有TDP-43病理的AD患者相比，具有TDP-43病理的AD患者具有增加的认知损害严重程度。此外，AD最常见的遗传风险因素载脂蛋白E4（APOE 4）与SDP-43病理发生频率增加相关。这些发现提供了强有力的证据，表明TDP-43病理学是多种神经退行性疾病（包括AD）的组成部分。在这里，我们回顾TDP-43的生物学和病理生物学，重点是它在AD中的作用。我们强调需要对导致TDP-43病理学的机制进行研究，特别是在与年龄相关的疾病如AD的情况下。
Transactive response DNA binding protein of 43 kDa (TDP-43) is an intranuclear protein encoded by the TARDBP gene that is involved in RNA splicing, trafficking, stabilization, and thus, the regulation of gene expression. Cytoplasmic inclusion bodies containing phosphorylated and truncated forms of TDP-43 are hallmarks of amyotrophic lateral sclerosis (ALS) and a subset of frontotemporal lobar degeneration (FTLD). Additionally, TDP-43 inclusions have been found in up to 57% of Alzheimer’s disease (AD) cases, most often in a limbic distribution, with or without hippocampal sclerosis. In some cases, TDP-43 deposits are also found in neurons with neurofibrillary tangles. AD patients with TDP-43 pathology have increased severity of cognitive impairment compared to those without TDP-43 pathology. Furthermore, the most common genetic risk factor for AD, apolipoprotein E4 (APOE4), is associated with increased frequency of TDP-43 pathology. These findings provide strong evidence that TDP-43 pathology is an integral part of multiple neurodegenerative conditions, including AD. Here, we review the biology and pathobiology of TDP-43 with a focus on its role in AD. We emphasize the need for studies on the mechanisms that lead to TDP-43 pathology, especially in the setting of age-related disorders such as AD.
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影响因子：
38.1
作者：
Chen-Plotkin, Alice S.;Lee, Virginia M. -Y.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
25
作者：
Chou CC;Zhang Y;Umoh ME;Vaughan SW;Lorenzini I;Liu F;Sayegh M;Donlin-Asp PG;Chen YH;Duong DM;Seyfried NT;Powers MA;Kukar T;Hales CM;Gearing M;Cairns NJ;Boylan KB;Dickson DW;Rademakers R;Zhang YJ;Petrucelli L;Sattler R;Zarnescu DC;Glass JD;Rossoll W
通讯作者：
Rossoll W
DOI：
10.1212/nxg.0000000000000080
发表时间：
2016-06
期刊：
Neurology. Genetics
影响因子：
--
作者：
Caroppo P;Camuzat A;Guillot-Noel L;Thomas-Antérion C;Couratier P;Wong TH;Teichmann M;Golfier V;Auriacombe S;Belliard S;Laurent B;Lattante S;Millecamps S;Clot F;Dubois B;van Swieten JC;Brice A;Le Ber I
通讯作者：
Le Ber I
影响因子：
4
作者：
Ayala, Youhna M.;Zago, Paola;Baralle, Francisco E.
通讯作者：
Baralle, Francisco E.
影响因子：
16.2
作者：
Alami NH;Smith RB;Carrasco MA;Williams LA;Winborn CS;Han SSW;Kiskinis E;Winborn B;Freibaum BD;Kanagaraj A;Clare AJ;Badders NM;Bilican B;Chaum E;Chandran S;Shaw CE;Eggan KC;Maniatis T;Taylor JP
通讯作者：
Taylor JP