MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ(25-35) -induced anxiety and cognitive deficits in a mouse model.
MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ(25-35) -induced anxiety and cognitive deficits in a mouse model.
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MGCD0103是一种选择性组蛋白脱乙酰基酶抑制剂，可在小鼠模型中辅助寡聚Aβ（25-35）诱导的焦虑和认知缺陷。
DOI：
10.1111/cns.13029
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发表时间：
2019-03
影响因子：
5.5
通讯作者：
Hsieh-Li HM
中科院分区：
文献类型：
--
作者：
Huang HJ;Huang HY;Hsieh-Li HM
Recently, histone deacetylase (HDAC) inhibitors are considered a possible therapeutic strategy in Alzheimer's disease (AD). However, HDACi treatments exhibit diverse functions with unfavorable effects in AD. Thus, the development of selective HDACi without side effects is urgently needed. HDACi, namely, BML210, MGCD0103, PXD101, and Droxinostat, were screened in mouse hippocampal primary cultures incubated with oligomeric Aβ25‐35 (50 μmol/L). MGCD0103 was chosen for in vivo tests and was intraperitoneally injected into C57BL/6J mice (0.5 mg/kg, once per day) for 4 weeks following an intrahippocampal CA1 injection of oligomeric Aβ25‐35. Brain samples were collected for pathological analyses after the behavioral analyses including open‐ field test (OFT), elevated plus maze (EPM), Y‐maze, and Morris water maze (MWM). Among the HDACi, MGCD0103 exhibited significant neuroprotection against the Aβ toxicity in primary cultures. MGCD0103 coattenuated cognitive deficits and anxiety against Aβ damage in mice. MGCD0103 further ameliorated pathological features such as the levels of acetylated histone 3 at Lys 9 site (H3K9) and α‐tubulin, synaptophysin, Aβ, tau protein phosphorylation, and serotonergic neuron loss against Aβ toxicity. Furthermore, chronic MGCD0103 treatment did not show liver or kidney toxicity in mice. These results reveal MGCD0103 could be a potential therapeutic agent against AD.
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影响因子：
6.1
作者：
Boumber Y;Younes A;Garcia-Manero G
通讯作者：
Garcia-Manero G
对复发或难治性淋巴瘤中的组蛋白脱乙酰基酶抑制剂的2阶段研究。
影响因子：
6.5
作者：
Batlevi CL;Crump M;Andreadis C;Rizzieri D;Assouline SE;Fox S;van der Jagt RHC;Copeland A;Potvin D;Chao R;Younes A
通讯作者：
Younes A
影响因子：
3.3
作者：
da Silva, P. F.;Garcia, V. A.;Schroeder, N.
通讯作者：
Schroeder, N.
影响因子：
15.9
作者：
Chuang, De-Maw;Leng, Yan;Marinova, Zoya;Kim, Hyeon-Ju;Chiu, Chi-Tso
通讯作者：
Chiu, Chi-Tso
影响因子：
3.1
作者：
Cuadrado-Tejedor, Mar;Ricobaraza, Ana L.;Garcia-Osta, Ana
通讯作者：
Garcia-Osta, Ana