Plasma membrane invaginations containing clusters of full-length PrPSc are an early form of prion-associated neuropathology in vivo.
Plasma membrane invaginations containing clusters of full-length PrPSc are an early form of prion-associated neuropathology in vivo.
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DOI：
10.1016/j.neurobiolaging.2012.12.015
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发表时间：
2013-06
影响因子：
4.2
通讯作者：
Peters PJ
中科院分区：
文献类型：
--
作者：
Godsave SF;Wille H;Pierson J;Prusiner SB;Peters PJ
在朊病毒疾病期间，细胞朊病毒蛋白（PrPC）重折叠成致病性同种型（PrPSc），其在中枢神经系统中积累并导致神经变性和死亡。我们使用免疫荧光，定量冷冻免疫金EM和断层扫描检测新生的，全长PrPSc在朊病毒感染的小鼠从早期临床前疾病阶段的海马。未感染和感染的大脑的比较表明，含有全长PrPSc的网站可以识别在neurophysiologic亮点和条纹的免疫荧光半薄（200 nm）的部分，并通过集群的冷冻免疫金EM标记。PrPSc被发现主要是在神经元质膜上，最引人注目的是在膜内陷和网站的细胞与细胞接触，是显而易见的接种后65天，或54%的潜伏期，以终端疾病。神经元的轴突和树突都受到影响。我们推测，紧密贴壁的质膜提供了一个有利的环境朊病毒转换和细胞间朊病毒转移。只有一小部分的成簇的PrP免疫金标记被发现在突触，表明突触不是针对朊病毒疾病。
During prion disease cellular prion protein (PrPC) is refolded into a pathogenic isoform (PrPSc) that accumulates in the central nervous system and causes neurodegeneration and death. We used immunofluorescence, quantitative cryo-immunogold EM and tomography to detect nascent, full-length PrPSc in the hippocampus of prion-infected mice from early pre-clinical disease stages onwards. Comparison of uninfected and infected brains showed that sites containing full-length PrPSc could be recognized in the neuropil by bright spots and streaks of immunofluorescence on semi-thin (200 nm) sections, and by clusters of cryo-immunogold EM labeling. PrPSc was found mainly on neuronal plasma membranes, most strikingly on membrane invaginations and sites of cell-to-cell contact, and was evident by 65 days postinoculation, or 54% of the incubation period to terminal disease. Both axons and dendrites in the neuropil were affected. We hypothesize that closely apposed plasma membranes provide a favourable environment for prion conversion and intercellular prion transfer. Only a small proportion of clustered PrP immunogold labeling was found at synapses, indicating that synapses are not targeted specifically in prion disease.
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影响因子：
16.6
作者：
Goold, R.;Rabbanian, S.;Sutton, L.;Andre, R.;Arora, P.;Moonga, J.;Clarke, A. R.;Schiavo, G.;Jat, P.;Collinge, J.;Tabrizi, S. J.
通讯作者：
Tabrizi, S. J.
影响因子：
6.7
作者：
Ermolayev V;Cathomen T;Merk J;Friedrich M;Härtig W;Harms GS;Klein MA;Flechsig E
通讯作者：
Flechsig E
影响因子：
6.1
作者：
Gray, Bryony C.;Siskova, Zuzana;O'Connor, Vincent
通讯作者：
O'Connor, Vincent
DOI：
10.1073/pnas.0308413101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Fevrier, B;Vilette, D;Raposo, G
通讯作者：
Raposo, G
影响因子：
5.3
作者：
Fuhrmann, Martin;Mitteregger, Gerda;Herms, Jochen
通讯作者：
Herms, Jochen