The ubiquitin-proteasome system in spongiform degenerative disorders.
The ubiquitin-proteasome system in spongiform degenerative disorders.
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DOI：
10.1016/j.bbadis.2008.08.006
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Chin LS
中科院分区：
文献类型：
--
作者：
Whatley BR;Li L;Chin LS
海绵状变性的特征是神经组织空泡化，伴有神经元死亡和神经胶质增生。虽然海绵状变性是朊病毒疾病的标志，但这种病理也存在于患有阿尔茨海默病、弥漫性路易体病、人类免疫缺陷病毒（HIV）感染和卡纳万海绵状脑白质营养不良的患者的脑中。这些不同疾病中海绵状变性的共同结果表明，共同的细胞机制必须是中枢神经系统海绵状变化和神经变性过程的基础。脑组织的免疫组织化学分析显示增加的泛素免疫反应性和周围地区的海绵状变化，表明参与的泛素-蛋白酶体系统功能障碍的发病机制海绵状神经变性。E3泛素-蛋白连接酶mahogunin环指蛋白-1（Mgrn 1）的无效突变导致动物海绵状神经变性的常染色体Recombinant遗传形式，这一发现加强了异常泛素化和海绵状神经变性之间的联系。最近的研究表明，异常的泛素化可以通过蛋白酶体依赖和非蛋白酶体依赖的机制改变细胞内信号和细胞功能，导致海绵状变性和神经元细胞死亡。进一步阐明海绵状神经变性的致病途径，将有助于开发治疗朊病毒疾病、HIV感染和其他海绵状变性疾病的新的合理疗法。
Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer’s disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan’s spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin–proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin–protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders.
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影响因子：
4.7
作者：
Biasini, E;Fioriti, L;Forloni, G
通讯作者：
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DOI：
10.1093/jnen/60.7.724
发表时间：
2001-07-01
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作者：
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通讯作者：
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DOI：
10.1111/j.1600-0749.2006.00340.x
发表时间：
2006-12-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
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通讯作者：
Gunn, Teresa M.