Levels of the Mahogunin Ring Finger 1 E3 ubiquitin ligase do not influence prion disease.
Levels of the Mahogunin Ring Finger 1 E3 ubiquitin ligase do not influence prion disease.
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DOI：
10.1371/journal.pone.0055575
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gunn TM
中科院分区：
文献类型：
--
作者：
Silvius D;Pitstick R;Ahn M;Meishery D;Oehler A;Barsh GS;DeArmond SJ;Carlson GA;Gunn TM
朊病毒病是罕见但总是致命的神经退行性疾病。它们与海绵状脑病有关，海绵状脑病是一种组织病理学，其特征是大脑神经毡中存在大型膜结合空泡结构。虽然主要原因被认为是正常形式的朊病毒蛋白 (PrPC) 转化为构象独特的致病形式 (PrPSc)，但导致海绵状变化、神经元功能障碍和死亡的细胞途径和机制尚不清楚。缺乏 Mahogunin Ring Finger 1 (MGRN1) E3 泛素连接酶的小鼠在 9 个月大时会出现海绵状脑病，但不会生病。据报道，在细胞培养中，细胞质中异常存在的 PrP 会与 MGRN1 相互作用并隔离。这导致了与 Mgrn1 表达被敲低时观察到的类似的内溶酶体运输缺陷，表明 MGRN1 依赖性运输在朊病毒疾病的发病机制中受到破坏。由于这些缺陷是通过 MGRN1 的过度表达来弥补的，因此我们研究了 Mgrn1 表达的降低或升高是否会影响接种 PrPSc 的小鼠疾病的发作、进展或病理学。没有观察到差异，表明 MGRN1 依赖性途径的破坏在传染性海绵状脑病的发病机制中没有发挥重要作用。
Prion diseases are rare but invariably fatal neurodegenerative disorders. They are associated with spongiform encephalopathy, a histopathology characterized by the presence of large, membrane-bound vacuolar structures in the neuropil of the brain. While the primary cause is recognized as conversion of the normal form of prion protein (PrPC) to a conformationally distinct, pathogenic form (PrPSc), the cellular pathways and mechanisms that lead to spongiform change, neuronal dysfunction and death are not known. Mice lacking the Mahogunin Ring Finger 1 (MGRN1) E3 ubiquitin ligase develop spongiform encephalopathy by 9 months of age but do not become ill. In cell culture, PrP aberrantly present in the cytosol was reported to interact with and sequester MGRN1. This caused endo-lysosomal trafficking defects similar to those observed when Mgrn1 expression is knocked down, implicating disrupted MGRN1-dependent trafficking in the pathogenesis of prion disease. As these defects were rescued by over-expression of MGRN1, we investigated whether reduced or elevated Mgrn1 expression influences the onset, progression or pathology of disease in mice inoculated with PrPSc. No differences were observed, indicating that disruption of MGRN1-dependent pathways does not play a significant role in the pathogenesis of transmissible spongiform encephalopathy.
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影响因子：
1.5
作者：
Jiao, Jian;Kim, Hae Young;Liu, Roy R.;Hogan, Carolyn A.;Sun, Kaihua;Tam, Lori Mon;Gunn, Teresa M.
通讯作者：
Gunn, Teresa M.
影响因子：
56.9
作者：
He, L;Lu, XY;Gunn, TM
通讯作者：
Gunn, TM
影响因子：
5.4
作者：
Norstrom, Eric M.;Ciaccio, Mark F.;Mastrianni, James A.
通讯作者：
Mastrianni, James A.
影响因子：
4.8
作者：
Fioriti, L;Dossena, S;Chiesa, R
通讯作者：
Chiesa, R
DOI：
10.1097/nen.0b013e3182544680
发表时间：
2012-05-01
影响因子：
3.2
作者：
Bajsarowicz, Krystyna;Ahn, Misol;DeArmond, Stephen J.
通讯作者：
DeArmond, Stephen J.