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胰岛素、肠促胰岛素及其他生长因子作为阿尔茨海默病和帕金森病潜在的新型治疗手段。

Insulin, incretins and other growth factors as potential novel treatments for Alzheimer's and Parkinson's diseases.

作者信息

Hölscher Christian

机构信息

*Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, U.K.

出版信息

Biochem Soc Trans. 2014 Apr;42(2):593-9. doi: 10.1042/BST20140016.

Abstract

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.

摘要

最近的研究表明,在阿尔茨海默病(AD)患者中,以及在一定程度上,帕金森病(PD)患者的胰岛素信号传导受损。这一发现引发了一系列研究项目,这些项目表明,使用最初开发用于治疗糖尿病的疗法能带来显著改善。临床前研究表明,应用胰岛素或长效肠促胰岛素类似物具有良好的神经保护作用。在AD和PD的转基因动物模型中,肠促胰岛素胰高血糖素样肽-1(GLP-1)的类似物可预防神经退行性过程,并改善AD和PD中的神经元及突触功能。在AD模型中,淀粉样斑块负荷、突触丧失以及认知障碍均得到改善,而在PD模型中,多巴胺能传递丧失和运动功能得以逆转。基于这些有前景的发现,正在进行多项临床试验,并且已经发表了首批令人鼓舞的临床结果。在针对AD患者的多项初步研究中,经鼻应用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患者的初步研究测试了一种目前作为2型糖尿病治疗药物上市的GLP-1受体激动剂,也显示出令人鼓舞的效果。目前还有其他几项针对AD患者的临床试验正在进行。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具有保护甚至恢复特性的新型治疗方法方面的巨大前景,而这些特性是目前任何药物治疗都无法提供的。

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