Diosgenin is an exogenous activator of 1,25D₃-MARRS/Pdia3/ERp57 and improves Alzheimer's disease pathologies in 5XFAD mice.
Diosgenin is an exogenous activator of 1,25D₃-MARRS/Pdia3/ERp57 and improves Alzheimer's disease pathologies in 5XFAD mice.
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DOI：
10.1038/srep00535
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发表时间：
2012
影响因子：
4.6
通讯作者：
Kuboyama, Tomoharu
中科院分区：
文献类型：
--
作者：
Tohda, Chihiro;Urano, Takuya;Umezaki, Masahito;Nemere, Ilka;Kuboyama, Tomoharu
本研究旨在探讨薯蓣皂苷元对阿尔茨海默病（AD）模型小鼠记忆障碍的影响及其作用机制。薯蓣皂苷元处理的5XFAD小鼠表现出显着改善的性能的对象识别记忆。薯蓣皂苷元治疗显着减少大脑皮层和海马中的淀粉样斑块和神经元缠结。变性轴突和突触前末梢，只观察到在区域密切相关的淀粉样蛋白斑块显着减少薯蓣皂苷元治疗。1，25 D3-膜相关的快速反应类固醇结合蛋白（1，25 D3-MARRS）被证明是薯蓣皂苷元的靶点。1，25 D3-MARRS敲低完全抑制薯蓣皂苷元诱导的皮质神经元轴突生长。在Aβ（1-42）诱导的轴突萎缩中，用抗1，25 D3-MARRS的中和抗体治疗可减弱薯蓣皂苷元的轴突再生作用。这是第一个证明外源性刺激剂薯蓣皂苷元激活1，25 D3-MARRS通路的研究，这可能是抗AD治疗的一个非常关键的信号靶标。
The aim of this study was to investigate the effects and the mechanism of diosgenin, a famous plant-derived steroidal sapogenin, on memory deficits in Alzheimer's disease (AD) model mice. Diosgenin-treated 5XFAD mice exhibited significantly improved performance of object recognition memory. Diosgenin treatment significantly reduced amyloid plaques and neurofibrillary tangles in the cerebral cortex and hippocampus. Degenerated axons and presynaptic terminals that were only observed in regions closely associated with amyloid plaques were significantly reduced by diosgenin treatment. The 1,25D3-membrane-associated, rapid response steroid-binding protein (1,25D3-MARRS) was shown to be a target of diosgenin. 1,25D3-MARRS knockdown completely inhibited diosgenin-induced axonal growth in cortical neurons. Treatment with a neutralizing antibody against 1,25D3-MARRS diminished the axonal regeneration effect of diosgenin in Aβ(1–42)-induced axonal atrophy. This is the first study to demonstrate that the exogenous stimulator diosgenin activates the 1,25D3-MARRS pathway, which may be a very critical signaling target for anti-AD therapy.
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影响因子：
16.2
作者：
Atwal, JK;Massie, B;Kaplan, DR
通讯作者：
Kaplan, DR
DOI：
10.1006/bbrc.1994.1714
发表时间：
1994-05-30
影响因子：
3.1
作者：
DORMANEN, MC;BISHOP, JE;NORMAN, AW
通讯作者：
NORMAN, AW
影响因子：
3.3
作者：
Lecanu, L.;Rammouz, G.;Papadopoulos, V.
通讯作者：
Papadopoulos, V.
影响因子：
4
作者：
Buitrago, Claudia G.;Arango, Nadia S.;Boland, Ricardo L.
通讯作者：
Boland, Ricardo L.
影响因子：
5.7
作者：
Chiu, Chuan-Sung;Chiu, Yung-Jia;Peng, Wen-Huang
通讯作者：
Peng, Wen-Huang