Nuclear localization of SMN and FUS is not altered in fibroblasts from patients with sporadic ALS.
Nuclear localization of SMN and FUS is not altered in fibroblasts from patients with sporadic ALS.
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DOI：
10.3109/21678421.2014.907319
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发表时间：
2014-12
影响因子：
2.8
通讯作者：
Mitsumoto H
中科院分区：
文献类型：
--
作者：
Kariya S;Sampson JB;Northrop LE;Luccarelli CM;Naini AB;Re DB;Hirano M;Mitsumoto H
散发性肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，没有确定的生物标志物。最近观察到家族性ALS患者和小鼠模型细胞中gems（运动神经元存活蛋白（SMN）阳性核小体）数量减少，表明SMN参与ALS病理学。在分子水平上，肉瘤融合蛋白（FUS）是家族性ALS相关蛋白之一，已被证明与SMN直接相互作用，而突变的FUS的核定位受损导致缺陷的gem形成。确定来自散发性ALS患者的皮肤来源的成纤维细胞中的gem和/或核FUS水平是否持续降低，从而可以构成该疾病的新的和容易获得的生物标志物。对20名患者和17名年龄匹配的健康对照的成纤维细胞进行培养，并对SMN和FUS进行免疫共染色。两组间Gems数目和FUS表达模式无差异。在ALS和对照组中，宝石的数量与活检时的年龄呈负相关。成纤维细胞中SMN和FUS的表达模式不能作为散发性ALS的生物标志物。供体年龄依赖性宝石减少是一个新的观察，SMN与细胞衰老。
Sporadic amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no established biological marker. Recent observation of a reduced number of gems (survival motor neuron protein (SMN)-positive nuclear bodies) in cells from patients with familial ALS and the mouse models suggests an involvement of SMN in ALS pathology. At a molecular level, fused in sarcoma (FUS), one of the familial ALS-linked proteins, has been demonstrated to directly interact with SMN, while impaired nuclear localization of mutated FUS causes defective gem formation. To determine whether gems and/or nuclear FUS levels in skin derived-fibroblasts from sporadic ALS patients are consistently reduced and thus could constitute a novel and readily-available biomarker of the disease. Fibroblasts from 20 patients and 17 age-matched healthy controls were cultured and co-immunostained for SMN and FUS. No difference was detected between two groups in the number of gems and in expression pattern of FUS. The number of gems negatively correlated with the age at biopsy in both ALS and control subjects. The expression pattern of SMN and FUS in fibroblasts cannot serve as a biomarker for sporadic ALS. Donor age-dependent gem reduction is a novel observation that links SMN with cellular senescence.
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影响因子：
64.5
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
通讯作者：
MELKI, J
影响因子：
4
作者：
Aston KI;Hunt SC;Susser E;Kimura M;Factor-Litvak P;Carrell D;Aviv A
通讯作者：
Aviv A
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：
4.4
作者：
Bhattacharya, Sujoy;Chaum, Edward;Johnson, Leonard R.
通讯作者：
Johnson, Leonard R.
影响因子：
3.5
作者：
Oketa, Y.;Higashida, K.;Ono, S.
通讯作者：
Ono, S.