Comparative analysis of autophagy and tauopathy related markers in cerebral ischemia and Alzheimer's disease animal models.
Comparative analysis of autophagy and tauopathy related markers in cerebral ischemia and Alzheimer's disease animal models.
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DOI：
10.3389/fnagi.2015.00084
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发表时间：
2015
影响因子：
4.8
通讯作者：
Cardona-Gomez GP
中科院分区：
文献类型：
--
作者：
Villamil-Ortiz JG;Cardona-Gomez GP
阿尔茨海默病（AD）和脑缺血（CI）是以tau蛋白聚集为特征的神经病理学，tau蛋白聚集是认知障碍和痴呆的标志。自噬失败可诱导蛋白质积累。自噬是一种参与细胞成分稳态循环的代谢途径。然而，自噬在这些tau蛋白病中的作用仍不清楚。在本研究中，我们使用3xTg-AD小鼠模型（年龄为6、12和18个月）和整体CI 2-VO（2-Vessel Occlusion）大鼠模型（缺血后1、15和30天）进行了比较分析，以鉴定AD和CI在短期、中期和长期进展期间产生的tau蛋白病中的自噬相关标志物。我们的研究结果证实了神经元的损失和过度磷酸化的tau聚集在躯体感觉皮层（SS-Cx）的3xTg-AD小鼠在后期（年龄18个月），这是支持失败的自噬。这些结果与在CI大鼠的SS-Cx中获得的结果相反，在CI大鼠中，我们在缺血后1天和15天检测到神经元损失和tau蛋白病，并且这种现象在30天被逆转。我们提出这种现象与晚期自噬诱导有关，因为数据显示p-mTOR活性降低，Beclin-1和Vps 34的关联，PHF-1的进行性减少，LC 3B斑点和自噬溶酶体形成增加。此外，生存途径未受影响。总之，我们的比较研究表明，自噬可以改善CI中的tau蛋白病，但不能改善AD中的tau蛋白病，这表明诱导神经保护和预防神经变性的不同时间方法。
Alzheimer’s disease (AD) and cerebral ischemia (CI) are neuropathologies that are characterized by aggregates of tau protein, a hallmark of cognitive disorder and dementia. Protein accumulation can be induced by autophagic failure. Autophagy is a metabolic pathway involved in the homeostatic recycling of cellular components. However, the role of autophagy in those tauopathies remains unclear. In this study, we performed a comparative analysis to identify autophagy related markers in tauopathy generated by AD and CI during short-term, intermediate, and long-term progression using the 3xTg-AD mouse model (aged 6,12, and 18 months) and the global CI 2-VO (2-Vessel Occlusion) rat model (1,15, and 30 days post-ischemia). Our findings confirmed neuronal loss and hyperphosphorylated tau aggregation in the somatosensory cortex (SS-Cx) of the 3xTg-AD mice in the late stage (aged 18 months), which was supported by a failure in autophagy. These results were in contrast to those obtained in the SS-Cx of the CI rats, in which we detected neuronal loss and tauopathy at 1 and 15 days post-ischemia, and this phenomenon was reversed at 30 days. We proposed that this phenomenon was associated with autophagy induction in the late stage, since the data showed a decrease in p-mTOR activity, an association of Beclin-1 and Vps34, a progressive reduction in PHF-1, an increase in LC3B puncta and autophago-lysosomes formation were observed. Furthermore, the survival pathways remained unaffected. Together, our comparative study suggest that autophagy could ameliorates tauopathy in CI but not in AD, suggesting a differential temporal approach to the induction of neuroprotection and the prevention of neurodegeneration.
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影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
DOI：
10.1186/alzrt5
发表时间：
2009-10-12
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Golde TE;Miller VM
通讯作者：
Miller VM
影响因子：
7.8
作者：
Caccamo A;Magrì A;Medina DX;Wisely EV;López-Aranda MF;Silva AJ;Oddo S
通讯作者：
Oddo S
影响因子：
9.9
作者：
Buchman, Aron S.;Yu, Lei;Bennett, David A.
通讯作者：
Bennett, David A.
影响因子：
82.9
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K