Insulin, incretins and other growth factors as potential novel treatments for Alzheimer's and Parkinson's diseases
Insulin, incretins and other growth factors as potential novel treatments for Alzheimer's and Parkinson's diseases
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DOI：
10.1042/bst20140016
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发表时间：
2014-04-01
影响因子：
3.9
通讯作者：
Hoelscher, Christian
中科院分区：
文献类型：
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作者：
Hoelscher, Christian
最近，研究表明，AD（阿尔茨海默病）患者和 PD（帕金森病）患者的胰岛素信号在某种程度上受损。这一发现启动了一系列研究项目，这些项目显示出使用最初开发用于治疗糖尿病的疗法取得了显着的进步。临床前研究表明，使用胰岛素或长效肠降血糖肽类似物具有良好的神经保护作用。在 AD 和 PD 转基因动物模型中，肠促胰岛素 GLP-1（胰高血糖素样肽 1）类似物可预防 AD 和 PD 的神经退行性过程并改善神经元和突触功能。 AD 模型中淀粉样斑块负荷、突触损失以及认知障碍得到改善，PD 模型中多巴胺能传递和运动功能的损失得到逆转。在这些有希望的发现的基础上，正在进行多项临床试验，并发布了第一个令人鼓舞的临床结果。在针对 AD 患者的几项试点研究中，经鼻注射胰岛素对认知和生物标志物显示出令人鼓舞的效果。一项针对 PD 患者的试点研究测试了目前市场上用于治疗 2 型糖尿病的 GLP-1 受体激动剂，也显示出令人鼓舞的效果。目前正在 AD 患者中进行其他几项临床试验。本综述总结了这些药物已证明的一系列神经保护作用，并强调了这种方法在提供新的治疗方法方面的巨大前景，这些治疗方法具有目前药物治疗无法提供的保护甚至恢复特性。
Recently, it has been shown that in patients with AD (Alzheimer's disease) and, to some degree, in patients with PD (Parkinson's disease) insulin signalling is impaired. This finding has initiated a range of research projects that showed remarkable improvements using treatments that initially had been developed to treat diabetes. Pre-clinical studies showed good neuroprotective effects when applying insulin or long-lasting analogues of incretin peptides. In transgenic animal models of AD and PD, analogues of the incretin GLP-1 (glucagon-like peptide 1) prevented neurodegenerative processes and improved neuronal and synaptic functionality in AD and PD. Amyloid plaque load and synaptic loss as well as cognitive impairment had been ameliorated in AD models, and dopaminergic loss of transmission and motor function was reversed in models of PD. On the basis of these promising findings, several clinical trials are being conducted with the first encouraging clinical results being published. In several pilot studies in AD patients, the nasal application of insulin showed encouraging effects on cognition and biomarkers. A pilot study in PD patients testing a GLP-1 receptor agonist that is currently on the market as a treatment for Type 2 diabetes also showed encouraging effects. Several other clinical trials are currently ongoing in AD patients. The present review summarizes the range of neuroprotective effects that these drugs have demonstrated and emphasizes the great promise that this approach has in providing novel treatments that have protective and even restorative properties that no current drug treatment can offer.