Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence.
Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence.
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DOI：
10.1007/s40263-013-0076-8
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发表时间：
2013-07
期刊：
影响因子：
6
通讯作者：
Benedict, Christian
中科院分区：
文献类型：
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作者：
Freiherr, Jessica;Hallschmid, Manfred;Frey, William H., II;Bruenner, Yvonne F.;Chapman, Colin D.;Hoelscher, Christian;Craft, Suzanne;De Felice, Fernanda G.;Benedict, Christian
在动物和人类中的研究已经将阿尔茨海默病（AD）与脑脊髓液胰岛素水平降低以及脑中胰岛素敏感性降低（胰岛素抵抗）相关联。这种现象伴随着胰岛素和胰岛素样生长因子的受体表达减弱，胰岛素受体底物-1的丝氨酸磷酸化增强，以及胰岛素穿过血脑屏障的转运受损。此外，临床试验已经证明，鼻内胰岛素改善患有AD或其前驱症状（轻度认知障碍）的患者的记忆表现和大脑的代谢完整性。这些结果与胰岛素减轻海马突触对β淀粉样蛋白（一种被认为是AD发生的病因的肽）的脆弱性的发现相结合，为假设支持脑胰岛素信号传导的药理学策略（如胰岛素鼻内给药）可能在治疗和预防AD方面具有重大潜力提供了强有力的理论基础。考虑到这一点，手头的审查将提出潜在的鼻内胰岛素的记忆增强和神经保护作用的分子机制。然后，我们将讨论鼻内胰岛素研究的结果，这些研究表明，增强大脑胰岛素信号传导可以改善认知健康和受损人类的记忆和学习过程。最后，我们将提供一个概述的神经影像学研究表明，在胰岛素代谢的障碍，如肥胖，2型糖尿病和AD的胰岛素抵抗和改变大脑对胰岛素的反应与脑容量减少，特别是海马萎缩。
Research in animals and humans has associated Alzheimer’s disease (AD) with decreased cerebrospinal fluid levels of insulin in combination with decreased insulin sensitivity (insulin resistance) in the brain. This phenomenon is accompanied by attenuated receptor expression of insulin and insulin-like growth factor, enhanced serine phosphorylation of insulin receptor substrate-1, and impaired transport of insulin across the blood-brain barrier. Moreover, clinical trials have demonstrated that intranasal insulin improves both memory performance and metabolic integrity of the brain in patients suffering from AD or its prodrome, mild cognitive impairment. These results, in conjunction with the finding that insulin mitigates hippocampal synapse vulnerability to beta amyloid, a peptide thought to be causative in the development of AD, provide a strong rationale for hypothesizing that pharmacological strategies bolstering brain insulin signaling, such as intranasal administration of insulin, could have significant potential in the treatment and prevention of AD. With this view in mind, the review at hand will present molecular mechanisms potentially underlying the memory-enhancing and neuroprotective effects of intranasal insulin. Then, we will discuss the results of intranasal insulin studies that have demonstrated that enhancing brain insulin signaling improves memory and learning processes in both cognitively healthy and impaired humans. Finally, we will provide an overview of neuroimaging studies indicating that disturbances in insulin metabolism—such as insulin resistance in obesity, type 2 diabetes and AD—and altered brain responses to insulin are linked to decreased cerebral volume and especially to hippocampal atrophy.
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DOI：
10.3233/jad-122308
发表时间：
2013
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Claxton A;Baker LD;Wilkinson CW;Trittschuh EH;Chapman D;Watson GS;Cholerton B;Plymate SR;Arbuckle M;Craft S
通讯作者：
Craft S
影响因子：
3.7
作者：
Benedict, C;Hallschmid, M;Kern, W
通讯作者：
Kern, W
影响因子：
--
作者：
Craft, Suzanne;Baker, Laura D.;Montine, Thomas J.;Minoshima, Satoshi;Watson, G. Stennis;Claxton, Amy;Arbuckle, Matthew;Callaghan, Maureen;Tsai, Elaine;Plymate, Stephen R.;Green, Pattie S.;Leverenz, James;Cross, Donna;Gerton, Brooke
通讯作者：
Gerton, Brooke
影响因子：
3.7
作者：
Chapman, Colin D.;Frey, William H., II;Craft, Suzanne;Danielyan, Lusine;Hallschmid, Manfred;Schithoth, Helgi B.;Benedict, Christian
通讯作者：
Benedict, Christian
影响因子：
14
作者：
通讯作者：
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