Heterogeneous ribonuclear protein A3 (hnRNP A3) is present in dipeptide repeat protein containing inclusions in Frontotemporal Lobar Degeneration and Motor Neurone disease associated with expansions in C9orf72 gene.
Heterogeneous ribonuclear protein A3 (hnRNP A3) is present in dipeptide repeat protein containing inclusions in Frontotemporal Lobar Degeneration and Motor Neurone disease associated with expansions in C9orf72 gene.
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DOI：
10.1186/s40478-017-0437-5
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发表时间：
2017-04-21
影响因子：
7.1
通讯作者：
Mann DMA
中科院分区：
文献类型：
--
作者：
Davidson YS;Flood L;Robinson AC;Nihei Y;Mori K;Rollinson S;Richardson A;Benson BC;Jones M;Snowden JS;Pickering-Brown S;Haass C;Lashley T;Mann DMA
额颞叶变性（FTLD）包括某些相关的神经退行性疾病，改变行为，个性和语言。异质性核糖核蛋白（hnRNP）维持RNA代谢，其功能的变化可能是FTLD发病机制的基础。对61例FTLD患者的颞叶皮质和海马切片进行hnRNP A1、A2/B1和A3免疫染色，根据病理学标志分为FTLD-tau和FTLD-TDP A、B和C型亚型，并根据遗传学分为C9 orf 72扩增、MAPT或GRN突变或无已知突变的患者。还研究了4例具有C9 orf 72扩增的运动神经元疾病（MND）患者和10名健康对照。半定量分析hnRNP在海马齿状回（DG）、CA 4区和颞叶皮质（Tcx）的表达强度。hnRNP A1、A2/B1和A3的免疫染色显示，在任何病理或遗传组中，生理染色的模式或量均无一致变化。在研究hnRNP A1、A2/B1和A3的任何FTLD病例中，在海马的Tcx或DG中均未观察到类似TDP-43免疫反应性神经元胞质内含物或营养不良性神经突的任何内含物的免疫染色。hnRNP A3免疫组化染色显示，在海马和小脑中未观察到类似于TDP-43阴性、p62免疫阳性的含有二肽重复蛋白（DPR）的包涵体。DG中hnRNP A3免疫反应阳性DPR的病例比例和病例中hnRNP A3阳性包涵体的数量显著高于CA 4区和小脑，但后者在所有三个区域中均显著低于p62免疫染色检测到的。本文的在线版本（doi：10.1186/s40478-017-0437-5）包含补充材料，可供授权用户使用。
Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter behaviour, personality and language. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP A1, A2/B1 and A3 was performed on sections of temporal cortex with hippocampus from 61 patients with FTLD, stratified by pathological hallmarks into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those without known mutation. Four patients with Motor Neurone Disease (MND) with C9orf72 expansions and 10 healthy controls were also studied. Semi-quantitative analysis assessed hnRNP staining intensity in dentate gyrus (DG) and CA4 region of hippocampus, and temporal cortex (Tcx) in the different pathological and genetic groups. Immunostaining for hnRNP A1, A2/B1 and A3 revealed no consistent changes in pattern or amount of physiological staining across any of the pathological or genetic groups. No immunostaining of any inclusions resembling TDP-43 immunoreactive neuronal cytoplasmic inclusions or dystrophic neurites, was seen in either Tcx or DG of the hippocampus in any of the FTLD cases investigated for hnRNP A1, A2/B1 and A3. However, immunostaining for hnRNP A3 showed that inclusion bodies, resembling those TDP-43 negative, p62-immunopositive structures containing dipeptide repeat proteins (DPR) were variably observed in hippocampus and cerebellum. The proportion of cases showing hnRNP A3-immunoreactive DPR, and the number of hnRNP A3-positive inclusions within cases, was significantly greater in DG than in cells of CA4 region and cerebellum, but the latter was significantly less in all three regions compared to that detected by p62 immunostaining. The online version of this article (doi:10.1186/s40478-017-0437-5) contains supplementary material, which is available to authorized users.