Prion protein on astrocytes or in extracellular fluid impedes neurodegeneration induced by truncated prion protein.
Prion protein on astrocytes or in extracellular fluid impedes neurodegeneration induced by truncated prion protein.
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DOI：
10.1016/j.expneurol.2009.03.017
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发表时间：
2009-06
影响因子：
5.3
通讯作者：
Chesebro, Bruce
中科院分区：
文献类型：
--
作者：
Race, Brent;Meade-White, Kimberly;Race, Richard;Baumann, Frank;Aguzzi, Adriano;Chesebro, Bruce
关键词：
朊病毒蛋白（PrP）是一种宿主编码的膜锚定糖蛋白，是对朊病毒疾病易感性所必需的。 PrP 对于正常的大脑功能（例如海马空间记忆）也可能很重要。先前表达氨基末端截短的小鼠 PrP (Δ32-134) 的转基因小鼠自发地患上一种与小脑颗粒神经元变性以及小脑深部和脑干白质空泡变性相关的致命疾病。这种疾病可以通过在神经元或少突胶质细胞上共表达野生型 (WT) 小鼠 PrP 来预防。在本实验中，我们研究了 Δ32–134 PrP 转基因小鼠，其 WT PrP 表达仅限于星形胶质细胞，星形胶质细胞是一种丰富的中枢神经系统细胞类型，对神经元活力至关重要。星形胶质细胞中 WT PrP 的表达足以使 50% 的小鼠免于疾病，并将另外 50% 的小鼠的生存期延长 200 天。我们还发现表达全长可溶性无锚 PrP 的转基因小鼠的存活率增加了 100 天。这两个结果共同表明，拯救 Δ32-134 PrP 诱导的神经变性可能涉及表达截短 PrP 的神经元和附近表达 WT PrP 或含有可溶性 WT PrP 的细胞外液的星形胶质细胞之间的相互作用。
Prion protein (PrP) is a host-encoded membrane-anchored glycoprotein which is required for susceptibility to prion disease. PrP may also be important for normal brain functions such as hippocampal spatial memory. Previously transgenic mice expressing amino terminally truncated mouse PrP (Δ32–134) spontaneously developed a fatal disease associated with degeneration of cerebellar granular neurons as well as vacuolar degeneration of deep cerebellar and brain stem white matter. This disease could be prevented by co-expression of wild-type (WT) mouse PrP on neurons or oligodendroglia. In the present experiments we studied Δ32–134 PrP transgenic mice with WT PrP expression restricted to astroglia, an abundant CNS cell-type important for neuronal viability. Expression of WT PrP in astroglia was sufficient to rescue 50% of mice from disease and prolonged survival by 200 days in the other 50%. We also found that transgenic mice expressing full-length soluble anchorless PrP had increased survival by 100 days. Together these two results indicated that rescue from neurodegeneration induced by Δ32–134 PrP might involve interactions between neurons expressing truncated PrP and nearby astrocytes expressing WT PrP or extracellular fluid containing soluble WT PrP.
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影响因子：
7.5
作者：
Priola, SA
通讯作者：
Priola, SA
影响因子：
5.4
作者：
Race, R;Oldstone, M;Chesebro, B
通讯作者：
Chesebro, B
影响因子：
9.9
作者：
BENDHEIM, PE;BROWN, HR;BOLTON, DC
通讯作者：
BOLTON, DC
影响因子：
6.1
作者：
Curtis, J;Errington, M;MacLeod, N
通讯作者：
MacLeod, N
影响因子：
56.9
作者：
Chesebro, B;Trifilo, M;Oldstone, M
通讯作者：
Oldstone, M