Lixisenatide reduces amyloid plaques, neurofibrillary tangles and neuroinflammation in an APP/PS1/tau mouse model of Alzheimer's disease
Lixisenatide reduces amyloid plaques, neurofibrillary tangles and neuroinflammation in an APP/PS1/tau mouse model of Alzheimer's disease
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Lixisenatide 可减少阿尔茨海默病 APP/PS1/tau 小鼠模型中的淀粉样斑块、神经原纤维缠结和神经炎症
DOI：
10.1016/j.bbrc.2017.11.114
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Qi, Jin-Shun
中科院分区：
文献类型：
--
作者：
Cai, Hong-Yan;Yang, Jun-Ting;Qi, Jin-Shun
2型糖尿病（T2DM）已被确定为阿尔茨海默病（AD）的高危因素。在AD大脑中发现了胰岛素信号的损伤。胰高血糖素样肽-1 （GLP-1）是一种肠促胰岛素激素，可使胰岛素信号正常化，并作为神经保护生长因子。我们之前已经证明长效GLP-1受体（GLP-1R）激动剂利昔那肽在大鼠的记忆形成、突触可塑性和细胞增殖中起重要作用。在后续研究中，我们分析了利利森那肽在12月龄APP/PS1/tau雌性小鼠和C57BL/6J雌性小鼠（作为对照）中以10 nmol/kg每日1次的剂量注射60 d后的神经保护作用及其机制。结果表明利昔那肽可减少12月龄APP/PS1/tau雌性小鼠海马淀粉样斑块、神经原纤维缠结和神经炎症；激活PKA-CREB信号通路和抑制p38-MAPK可能是利昔那肽发挥神经保护作用的重要机制。该研究表明，GLP-1R激动剂如利昔那肽可能有潜力发展成为一种新的治疗AD的药物。(C) 2017爱思唯尔公司版权所有。
Type 2 diabetes mellitus (T2DM) has been identified as a high risk factor for Alzheimer's disease (AD). The impairment of insulin signaling has been found in AD brain. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, normalises insulin signaling and acts as a neuroprotective growth factor. We have previously shown that the long-lasting GLP-1 receptor (GLP-1R) agonist lixisenatide plays an important role in memory formation, synaptic plasticity and cell proliferation of rats. In the follow-up study, we analysed the neuroprotective effect and mechanism of lixisenatide, injected for 60 days at 10 nmol/kg i.p. once daily in APP/PS1/tau female mice and C57BL/6J female mice (as control) aged 12 month. The results showed that lixisenatide could reduce amyloid plaques, neurofibrillary tangles and neuroinflammation in the hippocampi of 12-month-old APP/PS1/tau female mice; activation of PKA-CREB signaling pathway and inhibition of p38-MAPK might be the important mechanisms in the neuroprotective function of lixisenatide. The study demonstrated that GLP-1R agonists such as lixisenatide might have the potential to be developed as a novel therapy for AD. (C) 2017 Elsevier Inc. All rights reserved.