Kunesová Gabriela, Hlavácek Jan, Patocka Jirí, Evangelou Alexandra, Zikos Christos, Benaki Dimitra, Paravatou-Petsotas Maria, Pelecanou Maria, Livaniou Evangelia, Slaninova Jirina
Department of Toxicology, University of Defense, Trebesská 1575, 500 01 Hradec Králové, Czech Republic.
Peptides. 2008 Nov;29(11):1982-7. doi: 10.1016/j.peptides.2008.06.019. Epub 2008 Jul 5.
Humanin (HN) and its analogues have been shown to protect cells against death induced by various Alzheimer's disease (AD) genes and amyloid-beta-peptides in vitro; the analogues [Gly(14)]-HN and colivelin have also been shown to be potent in reversing learning and memory impairment induced by scopolamine or quinuclidinyl benzilate (QNB) in mice or rats in vivo using the Y-maze or multiple T-maze tests. This paper describes the activity of new peptides of the HN family, after i.p. administration, on QNB-induced impairment of spatial memory in the multiple T-maze test in rats. The following peptides have been studied: HN analogues truncated either on the C- or N-terminus, or analogues having a tert-Leu in place of Leu in the central part of the molecule, the active HN core PAGASRLLLLTGEIDLP (RG-PAGA) and its analogues having three or five leucines instead of four, and finally the recently described hybrid peptide colivelin (i.e. a peptide having the activity-dependent neurotrophic factor SALLRSIPA attached to the N-terminus of the active RG-PAGA) and its des-Leu- and plus-Leu-analogues. While the truncated analogues and most of the tert-Leu containing analogues were devoid of activity, the analogues of the RG-PAGA were active, i.e. they reversed the impairment of spatial memory irrespective of the number of Leu present in their sequence. The highest activity was shown by colivelin and its des-Leu-analogue. These results demonstrate the potential of HN analogues in the modulation of the cholinergic system, which plays an important role in the cognitive deficits associated with AD and other neurodegenerative diseases.
人胰岛素（HN）及其类似物已被证明在体外可保护细胞免受各种阿尔茨海默病（AD）基因和β-淀粉样肽诱导的死亡；类似物[Gly(14)]-HN和可力维林也已被证明在使用Y迷宫或多重T迷宫试验的体内实验中，对由东莨菪碱或喹核酯（QNB）诱导的小鼠或大鼠学习和记忆障碍具有显著的逆转作用。本文描述了HN家族新肽经腹腔注射后，在大鼠多重T迷宫试验中对QNB诱导的空间记忆损伤的活性。研究了以下几种肽：C端或N端截短的HN类似物，或在分子中部用叔亮氨酸取代亮氨酸的类似物，活性HN核心肽PAGASRLLLLTGEIDLP（RG-PAGA）及其具有三个或五个亮氨酸而非四个亮氨酸的类似物，以及最近描述的杂合肽可力维林（即一种将活性依赖性神经营养因子SALLRSIPA连接到活性RG-PAGA的N端的肽）及其去亮氨酸和加亮氨酸类似物。虽然截短的类似物和大多数含叔亮氨酸的类似物没有活性，但RG-PAGA的类似物具有活性，即无论其序列中亮氨酸的数量如何，它们都能逆转空间记忆损伤。可力维林及其去亮氨酸类似物表现出最高活性。这些结果证明了HN类似物在调节胆碱能系统方面的潜力，胆碱能系统在与AD和其他神经退行性疾病相关的认知缺陷中起重要作用。
