Amylin and its analogs: a friend or foe for the treatment of Alzheimer's disease?
Amylin and its analogs: a friend or foe for the treatment of Alzheimer's disease?
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DOI：
10.3389/fnagi.2014.00186
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发表时间：
2014
影响因子：
4.8
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Qiu WQ;Zhu H
Amylin是一种肠-脑轴激素，而淀粉样β肽（a β）是阿尔茨海默病（AD）大脑的主要组成部分，它们有几个共同的特征，包括相似的β-片二级结构，与相同的受体结合，并被相同的蛋白酶，胰岛素降解酶（IDE）降解。然而，尽管胰淀素很容易穿过血脑屏障（BBB）并介导几种活动，包括改善葡萄糖代谢、放松脑血管结构、调节炎症反应和可能增强神经再生，但Aβ没有已知的生理功能。因此，AD大脑中丰富的Aβ可以阻断或干扰胰淀素与其受体的结合并阻碍其功能。近年来对AD动物模型的研究表明，胰淀素及其类似物可减轻AD脑病理，改善AD患者的认知障碍。鉴于，除了淀粉样斑块和神经原纤维缠结外，脑糖代谢紊乱和脑血管损伤是AD大脑的标志，我们提出给予外源性胰淀素型肽有可能成为AD诊断和治疗的新途径。尽管胰淀素的自聚集特性可能限制了其作为AD治疗药物的发展，但其临床类似物，与胰淀素含有3个氨基酸差异的普兰林肽，不像人类胰淀素那样聚集，但更有效地介导胰淀素在大脑中的活动。普兰林肽是一种治疗糖尿病的有效药物，具有良好的安全性。因此，应该进行随机、双盲、安慰剂对照的临床试验来检验普兰林肽治疗AD的疗效。本文综述了胰淀素型肽的知识和发现，并讨论了其潜在的AD的利弊。
Amylin, a gut-brain axis hormone, and amyloid-beta peptides (Aβ), a major component of the Alzheimer's disease (AD) brain, share several features, including similar β-sheet secondary structures, binding to the same receptor and being degraded by the same protease, insulin degrading enzyme (IDE). However, while amylin readily crosses the blood brain barrier (BBB) and mediates several activities including improving glucose metabolism, relaxing cerebrovascular structure, modulating inflammatory reaction and perhaps enhancing neural regeneration, Aβ has no known physiological functions. Thus, abundant Aβ in the AD brain could block or interfere with the binding of amylin to its receptor and hinder its functions. Recent studies using animal models for AD demonstrate that amylin and its analog reduce the AD pathology in the brain and improve cognitive impairment in AD. Given that, in addition to amyloid plaques and neurofibrillary tangles, perturbed cerebral glucose metabolism and cerebrovascular damage are the hallmarks of the AD brain, we propose that giving exogenous amylin type peptides have the potential to become a new avenue for the diagnosis and therapeutic of AD. Although amylin's property of self-aggregation may be a limitation to developing it as a therapeutic for AD, its clinical analog, pramlintide containing 3 amino acid differences from amylin, does not aggregate like human amylin, but more potently mediates amylin's activities in the brain. Pramlintide is an effective drug for diabetes with a favorable profile of safety. Thus a randomized, double-blind, placebo-controlled clinical trial should be conducted to examine the efficacy of pramlintide for AD. This review summarizes the knowledge and findings on amylin type peptides and discuss pros and cons for their potential for AD.
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影响因子：
46.2
作者：
DeToma AS;Salamekh S;Ramamoorthy A;Lim MH
通讯作者：
Lim MH
影响因子：
6.1
作者：
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Amico-Roxas, Matilde
DOI：
10.1073/pnas.84.23.8628
发表时间：
1987-12-01
影响因子：
11.1
作者：
COOPER, GJS;WILLIS, AC;REID, KBM
通讯作者：
REID, KBM
影响因子：
3.2
作者：
Andreetto, Erika;Yan, Li-Mei;Kapurniotu, Aphrodite
通讯作者：
Kapurniotu, Aphrodite
DOI：
10.1152/ajpendo.1998.275.4.e694
发表时间：
1998-10-01
影响因子：
5.1
作者：
Cornish, J;Callon, KE;Reid, IR
通讯作者：
Reid, IR