The reduction of astrocytic tau prevents amyloid-β-induced synaptotoxicity.
The reduction of astrocytic tau prevents amyloid-β-induced synaptotoxicity.
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DOI：
10.1093/braincomms/fcac235
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发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
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阿尔茨海默病是一种神经系统疾病，其特征是β淀粉样蛋白的过度产生和聚集以及tau蛋白的磷酸化和神经元内积累。这些事件促进突触功能障碍和丧失，导致神经变性和认知缺陷。星形胶质细胞与突触密切相关，在病理条件下被激活，具有神经毒性并对突触产生不利影响。虽然已经确定减少神经元tau表达可以防止淀粉样蛋白诱导的毒性，但星形细胞tau在这种情况下的作用仍未得到充分研究。在此，我们进行了一系列星形胶质细胞和神经元原代培养，以评估星形胶质细胞tau水平降低对星形胶质细胞介导的淀粉样蛋白诱导的突触变性的影响。我们的研究结果表明，星形胶质细胞中tau蛋白的下调减轻了它们暴露于β淀粉样蛋白引发的突触损失。此外，星形胶质细胞中tau的缺失促进了几种突触保护基因的上调，随后增加了神经保护因子penttraxin 3的产生。这些结果扩大了我们对星形细胞tau在淀粉样蛋白刺激诱导的神经退行性过程中的作用的理解，以及减少星形细胞tau如何通过刺激突触保护因子的表达来改善星形细胞功能。减少内源性星形细胞tau表达可能是预防阿尔茨海默病和其他神经系统疾病突触损伤的潜在策略。Cisternas等人报道了星形胶质细胞中tau蛋白的下调如何减轻由β淀粉样蛋白暴露引发的突触损失。作者认为，星形胶质细胞中tau的缺失促进了一系列突触保护基因（如pentaxin3）的上调。
Alzheimer’s disease is a neurological disorder characterized by the overproduction and aggregation of amyloid-beta and the phosphorylation and intraneuronal accumulation of tau. These events promote synaptic dysfunction and loss, leading to neurodegeneration and cognitive deficits. Astrocytes are intimately associated with synapses and become activated under pathological conditions, becoming neurotoxic and detrimentally affecting synapses. Although it has been established that reducing neuronal tau expression prevents amyloid-beta-induced toxicity, the role of astrocytic tau in this setting remains understudied. Herein, we performed a series of astrocytic and neuronal primary cultures to evaluate the effects of decreasing astrocytic tau levels on astrocyte-mediated amyloid-beta-induced synaptic degeneration. Our results suggest that the downregulation of tau in astrocytes mitigates the loss of synapses triggered by their exposure to amyloid-beta. Additionally, the absence of tau from astrocytes promotes the upregulation of several synaptoprotective genes, followed by increased production of the neuroprotective factor Pentraxin 3. These results expand our understanding of the contribution of astrocytic tau to the neurodegenerative process induced by amyloid-beta-stimulation and how reducing astrocytic tau could improve astrocyte function by stimulating the expression of synaptoprotective factors. Reducing endogenous astrocytic tau expression could be a potential strategy to prevent synaptic damage in Alzheimer's disease and other neurological conditions. Cisternas et al. reported how the downregulation of tau in astrocytes mitigates the loss of synapses triggered by their exposure to amyloid-beta. The authors suggested that the absence of tau from astrocytes promotes the upregulation of a series of synaptoprotective genes such as Pentraxin 3.
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影响因子：
4.3
作者：
DeVos SL;Corjuc BT;Oakley DH;Nobuhara CK;Bannon RN;Chase A;Commins C;Gonzalez JA;Dooley PM;Frosch MP;Hyman BT
通讯作者：
Hyman BT
影响因子：
16.6
作者：
Bi M;Gladbach A;van Eersel J;Ittner A;Przybyla M;van Hummel A;Chua SW;van der Hoven J;Lee WS;Müller J;Parmar J;Jonquieres GV;Stefen H;Guccione E;Fath T;Housley GD;Klugmann M;Ke YD;Ittner LM
通讯作者：
Ittner LM
影响因子：
14.8
作者：
Beaudoin, Gerard M. J., III;Lee, Seung-Hye;Arikkath, Jyothi
通讯作者：
Arikkath, Jyothi
影响因子：
5.3
作者：
DeVos, Sarah L.;Goncharoff, Dustin K.;Miller, Timothy M.
通讯作者：
Miller, Timothy M.
星形胶质细胞是Aβ诱导的神经毒性和TAU磷酸化的重要介体。
影响因子：
9
作者：
通讯作者：
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