Small Heat Shock Protein 22 Improves Cognition and Learning in the Tauopathic Brain.
Small Heat Shock Protein 22 Improves Cognition and Learning in the Tauopathic Brain.
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DOI：
10.3390/ijms23020851
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发表时间：
2022-01-13
影响因子：
5.6
通讯作者：
Blair LJ
中科院分区：
文献类型：
--
作者：
Rodriguez Ospina S;Blazier DM;Criado-Marrero M;Gould LA;Gebru NT;Beaulieu-Abdelahad D;Wang X;Remily-Wood E;Chaput D;Stevens S;Uversky VN;Bickford PC;Dickey CA;Blair LJ
微管相关蛋白tau在阿尔茨海默病(AD)和其他tau病中病理性地聚集和聚集，导致认知功能障碍和神经元丢失。分子伴侣，如小的热休克蛋白(SHsps)，可以帮助阻止错误折叠的蛋白质的积累，如tau。在这里，我们测试了一种假说，即过表达野生型Hsp22(WtHsp22)及其仿磷酸型(S24，57D)Hsp22突变体(MtHsp22)可以减缓tau的积累并保存记忆。我们的结果表明，HSP22可以保护自发性脑内突触可塑性和认知功能的缺陷。然而，我们没有在这些小鼠中检测到tau磷酸化或水平的显著变化。这导致我们假设，由于在表达wtHsp22或mtHsp22的非转基因小鼠中没有测量到显著的益处，因此tau转基因小鼠的功能益处是通过恢复tau转基因小鼠海马区的功能通路实现的。为了确定这些途径，我们对注射部位的组织裂解物进行了质谱分析。总体而言，我们的数据显示，Hsp22在神经元中的过表达通过调节典型路径和上游调节因子来促进突触可塑性，这些调节因子被描述为潜在的AD标志物和突触发生调节因子，如eIF4E和NFKBIA。
The microtubule-associated protein tau pathologically accumulates and aggregates in Alzheimer’s disease (AD) and other tauopathies, leading to cognitive dysfunction and neuronal loss. Molecular chaperones, like small heat-shock proteins (sHsps), can help deter the accumulation of misfolded proteins, such as tau. Here, we tested the hypothesis that the overexpression of wild-type Hsp22 (wtHsp22) and its phosphomimetic (S24,57D) Hsp22 mutant (mtHsp22) could slow tau accumulation and preserve memory in a murine model of tauopathy, rTg4510. Our results show that Hsp22 protected against deficits in synaptic plasticity and cognition in the tauopathic brain. However, we did not detect a significant change in tau phosphorylation or levels in these mice. This led us to hypothesize that the functional benefit was realized through the restoration of dysfunctional pathways in hippocampi of tau transgenic mice since no significant benefit was measured in non-transgenic mice expressing wtHsp22 or mtHsp22. To identify these pathways, we performed mass spectrometry of tissue lysates from the injection site. Overall, our data reveal that Hsp22 overexpression in neurons promotes synaptic plasticity by regulating canonical pathways and upstream regulators that have been characterized as potential AD markers and synaptogenesis regulators, like EIF4E and NFKBIA.
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影响因子：
12.4
作者：
Carty, Niki C.;Nash, Kevin;Morgan, Dave
通讯作者：
Morgan, Dave
影响因子：
3.4
作者：
Blair, Laura J.;Criado-Marrero, Marangelie;Dickey, Chad A.
通讯作者：
Dickey, Chad A.
影响因子：
7.1
作者：
Criado-Marrero M;Gebru NT;Blazier DM;Gould LA;Baker JD;Beaulieu-Abdelahad D;Blair LJ
通讯作者：
Blair LJ
DOI：
10.1523/jneurosci.2456-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Boersma MC;Dresselhaus EC;De Biase LM;Mihalas AB;Bergles DE;Meffert MK
通讯作者：
Meffert MK
DOI：
10.1073/pnas.91.6.2076
发表时间：
1994-03-15
影响因子：
11.1
作者：
BOBO, RH;LASKE, DW;OLDFIELD, EH
通讯作者：
OLDFIELD, EH