Optineurin in neurodegenerative diseases
Optineurin in neurodegenerative diseases
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DOI：
10.1111/j.1440-1789.2011.01199.x
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发表时间：
2011-12-01
期刊：
影响因子：
2.3
通讯作者：
Okamoto, Koichi
中科院分区：
文献类型：
--
作者：
Osawa, Tenshi;Mizuno, Yuji;Okamoto, Koichi
opopineurin是一种与正常张力性青光眼和原发性开角型青光眼相关的基因，是不可逆双侧失明的主要原因之一。最近，在肌萎缩性侧索硬化症（ALS）患者中发现了编码优神经蛋白的基因突变。免疫组化分析显示脊髓束状包涵体和圆形透明包涵体中有optinurin聚集，提示optinurin可能是ALS更普遍的标志物。然而，我们的详细检查表明，optineurin不仅存在于ALS相关的病理结构中，还存在于ALS伴痴呆的泛素阳性神经元内包涵体、ALS嗜碱性型的嗜碱性包涵体、阿尔茨海默病的神经原纤维缠结和营养不良的神经突、帕金森病的路易体和路易神经突、克雅氏病的肿胀神经元、多系统萎缩的胶质细胞质包涵体、在疾病中挑选尸体。对于优神经蛋白阳性的亲碱性包体，这些结构对泛素表现出不同的免疫反应性；一些结构呈明显的泛素阳性，而另一些则呈蛋白阴性，这表明optinurin的表达并不总是与泛素的表达相关。本研究表明，opopineurin在神经退行性疾病中广泛分布；然而，它的意义是模糊的。
Optineurin is a gene associated with normal tension glaucoma and primary open-angle glaucoma, one of the major causes of irreversible bilateral blindness. Recently, mutations in the gene encoding optineurin were found in patients with amyotrophic lateral sclerosis (ALS). Immunohistochemical analysis showed aggregation of optineurin in skein-like inclusions and round hyaline inclusions in the spinal cord, suggesting that optineurin appears to be a more general marker for ALS. However, our detailed examinations demonstrated that optineurin was found not only in ALS-associated pathological structures, but also in ubiquitin-positive intraneuronal inclusions in ALS with dementia, basophilic inclusions in the basophilic type of ALS, neurofibrillary tangles and dystrophic neurites in Alzheimer's disease, Lewy bodies and Lewy neurites in Parkinson's disease, ballooned neurons in Creutzfeldt-Jakob disease, glial cytoplasmic inclusions in multiple system atrophy, and Pick bodies in Pick disease. With respect to optineurin-positive basophilic inclusions, these structures showed variable immunoreactivities for ubiquitin; some structures were obviously ubiquitin-positive, while others were negative for the protein, suggesting that optineurin expression was not always associated with the expression of ubiquitin. This study indicates that optineurin is widely distributed in neurodegenerative conditions; however, its significance is obscure.