Osmotin attenuates amyloid beta-induced memory impairment, tau phosphorylation and neurodegeneration in the mouse hippocampus.
Osmotin attenuates amyloid beta-induced memory impairment, tau phosphorylation and neurodegeneration in the mouse hippocampus.
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DOI：
10.1038/srep11708
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发表时间：
2015-06-29
影响因子：
4.6
通讯作者：
Kim MO
中科院分区：
文献类型：
--
作者：
Ali T;Yoon GH;Shah SA;Lee HY;Kim MO
阿尔茨海默病(AD)的病理特征包括淀粉样β蛋白(Aβ)堆积、神经原纤维缠结形成、突触功能障碍和神经元丢失。在这项研究中，我们研究了新型渗透素的神经保护作用，渗透素是从烟草中提取的一种植物蛋白，被认为是哺乳动物脂联素的同源物。在这里，我们观察到在脑室注射A μ1-42后3天和40天用渗透素(15 g/g，腹腔注射，4β小时)治疗显著改善了Aβ1-42引起的小鼠记忆障碍。这些结果表明，渗透素能逆转Aβ1-42注射所致的突触缺失、Aβ积聚和BACE1的表达。渗透素能通过调节p-β3K、p-Akt(丝氨酸473)和p-GSK3β(丝氨酸9)的异常磷酸化，减轻A GSK1-42诱导的tau蛋白在丝氨酸413的过度磷酸化。此外，我们的免疫印迹和免疫组织化学结果表明，渗透素阻止了Aβ1-42诱导的Aβ1-42处理的小鼠的细胞凋亡和神经变性。此外，渗透素在体外可减轻Aβ1-42诱导的神经毒性。据我们所知，这项研究是首次研究一种新的渗透素对Aβ1-42诱导的神经毒性的神经保护作用。我们的结果表明，这种普遍存在的植物蛋白可能成为一种新的、有前途的和可获得的神经保护剂，用于治疗进行性神经退行性疾病，如AD。
The pathological hallmarks of Alzheimer’s disease (AD) include amyloid beta (Aβ) accumulation, neurofibrillary tangle formation, synaptic dysfunction and neuronal loss. In this study, we investigated the neuroprotection of novel osmotin, a plant protein extracted from Nicotiana tabacum that has been considered to be a homolog of mammalian adiponectin. Here, we observed that treatment with osmotin (15 μg/g, intraperitoneally, 4 hr) at 3 and 40 days post-intracerebroventricular injection of Aβ1-42 significantly ameliorated Aβ1-42-induced memory impairment in mice. These results revealed that osmotin reverses Aβ1-42 injection-induced synaptic deficits, Aβ accumulation and BACE-1 expression. Treatment with osmotin also alleviated the Aβ1-42-induced hyperphosphorylation of the tau protein at serine 413 through the regulation of the aberrant phosphorylation of p-PI3K, p-Akt (serine 473) and p-GSK3β (serine 9). Moreover, our western blots and immunohistochemical results indicated that osmotin prevented Aβ1-42-induced apoptosis and neurodegeneration in the Aβ1-42-treated mice. Furthermore, osmotin attenuated Aβ1-42-induced neurotoxicity in vitro. To our knowledge, this study is the first to investigate the neuroprotective effect of a novel osmotin against Aβ1-42-induced neurotoxicity. Our results demonstrated that this ubiquitous plant protein could potentially serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.
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DOI：
10.1016/j.bbrc.2006.02.186
发表时间：
2006-05-05
影响因子：
3.1
作者：
Jung, TW;Lee, JY;Cha, BS
通讯作者：
Cha, BS
影响因子：
2.1
作者：
Ferrer, I.;Gomez-Isla, T.;Avila, J.
通讯作者：
Avila, J.
影响因子：
4.8
作者：
Diniz, Breno S.;Teixeira, Antonio L.;Forlenza, Orestes V.
通讯作者：
Forlenza, Orestes V.
影响因子：
4.7
作者：
Culmsee, C;Zhu, XX;Mattson, MP
通讯作者：
Mattson, MP
影响因子：
4.8
作者：
Chandrasekar, Bysani;Boylston, William H.;Valente, Anthony J.
通讯作者：
Valente, Anthony J.