Prion-like acceleration of a synucleinopathy in a transgenic mouse model
Prion-like acceleration of a synucleinopathy in a transgenic mouse model
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DOI：
10.1016/j.neurobiolaging.2011.06.022
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Baron, Thierry
中科院分区：
文献类型：
--
作者：
Mougenot, Anne-Laure;Nicot, Simon;Baron, Thierry
我们在这项研究中的目的是实验研究可能在体内传播的突触核蛋白病，使用转基因小鼠模型（TgM 83）表达的人A53 T突变的α-突触核蛋白。将来自老年TgM 83小鼠的脑匀浆脑内接种到年轻TgM 83小鼠中，所述老年TgM 83小鼠显示由于突触核蛋白病引起的运动临床体征并且含有不溶性和磷酸化（pSer 129）α-突触核蛋白。与未接种的TgM 83小鼠或接种了来自年轻健康TgM 83小鼠的脑匀浆的小鼠相比，这引发了特征性运动临床体征的早期发作。这种早期疾病与Ser 129上磷酸化的不溶性α-突触核蛋白相关，正如已经在年老和患病的未接种TgM 83转基因小鼠中鉴定的那样。尽管分子机制仍有待确定，但在用来自受突触核蛋白病影响的小鼠的组织接种表达人突变α-突触核蛋白的小鼠后，病理学的加速可能与疾病的“朊病毒样”传播一致。(C)2012 Elsevier Inc. All rights reserved.
Our aim in this study was to investigate experimentally the possible in vivo transmission of a synucleinopathy, using a transgenic mouse model (TgM83) expressing the human A53T mutated alpha-synuclein. Brain homogenates from old TgM83 mice showing motor clinical signs due to the synucleinopathy and containing insoluble and phosphorylated (pSer129) alpha-synuclein were intracerebrally inoculated in young TgM83 mice. This triggered an early onset of characteristic motor clinical signs, compared with uninoculated TgM83 mice or to mice inoculated with a brain homogenate from a young, healthy TgM83 mouse. This early disease was associated with insoluble alpha-synuclein phosphorylated on Ser129, as already identified in old and sick uninoculated TgM83 transgenic mice. Although the molecular mechanisms remain to be determined, acceleration of the pathology following inoculation of mice expressing human mutated alpha-synuclein with tissues from mice affected by the synucleinopathy, could be consistent with "prion-like" propagation of the disease. (C) 2012 Elsevier Inc. All rights reserved.