Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease.
Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease.
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DOI：
10.1007/s00401-009-0581-5
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发表时间：
2009-11
影响因子：
12.7
通讯作者：
Mackenzie IR
中科院分区：
文献类型：
--
作者：
Neumann M;Roeber S;Kretzschmar HA;Rademakers R;Baker M;Mackenzie IR
神经元中间丝包涵体病(NIFID)是一种罕见的神经退行性疾病，通常表现为早发性、散发性额颞叶痴呆(FTD)，并伴有锥体和/或锥体外系运动障碍。神经病理学的特点是额颞叶变性，伴有神经元包涵体，所有IV类中间丝(IF)、轻、中、重神经细丝亚单位和α-Interexin均呈免疫反应。然而，NIFID中并不是所有的包裹体都是IF阳性的，初级分子缺陷仍然不确定。编码融合肉瘤(FUS)蛋白的基因突变最近被确定为家族性肌萎缩侧索硬化症(ALS)的原因之一。由于FTD和ALS之间存在临床、遗传和病理上的重叠，我们研究了FUS在NIFID中的可能作用。我们发现细胞内异常积聚的FUS是我们NIFID病例(n=5)的一致特征。FUS免疫组织化学标记的神经元包涵体比IF多。几种类型的包涵体始终为FUS阳性，但IF阴性，包括神经元核内包涵体和神经胶质细胞质包涵体。双标记免疫荧光证实，许多细胞只有FUS阳性包涵体，所有IF阳性包涵体的细胞也含有病理性FUS。在一个有DNA的病例中没有发现FUS基因的突变。提示FUS在NIFID的发病机制中可能起重要作用。
Neuronal intermediate filament inclusion disease (NIFID) is an uncommon neurodegenerative condition that typically presents as early-onset, sporadic frontotemporal dementia (FTD), associated with a pyramidal and/or extrapyramidal movement disorder. The neuropathology is characterized by frontotemporal lobar degeneration with neuronal inclusions that are immunoreactive for all class IV intermediate filaments (IF), light, medium and heavy neurofilament subunits and α-internexin. However, not all the inclusions in NIFID are IF-positive and the primary molecular defect remains uncertain. Mutations in the gene encoding the fused in sarcoma (FUS) protein have recently been identified as a cause of familial amyotrophic lateral sclerosis (ALS). Because of the recognized clinical, genetic and pathological overlap between FTD and ALS, we investigated the possible role of FUS in NIFID. We found abnormal intracellular accumulation of FUS to be a consistent feature of our NIFID cases (n = 5). More neuronal inclusions were labeled using FUS immunohistochemistry than for IF. Several types of inclusions were consistently FUS-positive but IF-negative, including neuronal intranuclear inclusions and glial cytoplasmic inclusions. Double-label immunofluorescence confirmed that many cells had only FUS-positive inclusions and that all cells with IF-positive inclusions also contained pathological FUS. No mutations in the FUS gene were identified in a single case with DNA available. These findings suggest that FUS may play an important role in the pathogenesis of NIFID.
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影响因子：
--
作者：
Andersson MK;Ståhlberg A;Arvidsson Y;Olofsson A;Semb H;Stenman G;Nilsson O;Aman P
通讯作者：
Aman P
影响因子：
56.9
作者：
Kwiatkowski, T. J., Jr.;Bosco, D. A.;Brown, R. H., Jr.
通讯作者：
Brown, R. H., Jr.
影响因子：
6
作者：
Cairns, NJ;Zhukareva, V;Trojanowski, JQ
通讯作者：
Trojanowski, JQ
DOI：
10.1093/bfgp/ell015
发表时间：
2006-03-01
期刊：
Briefings in Functional Genomics & Proteomics
影响因子：
--
作者：
Law, Warren J.;Cann, Kendra L.;Hicks, Geoffrey G.
通讯作者：
Hicks, Geoffrey G.
影响因子：
12.7
作者：
Cairns, NJ;Uryu, K;Trojanowski, JQ
通讯作者：
Trojanowski, JQ