新型CARTp类似物在THY-Tau22小鼠海马中的神经保护作用

IF 4.6 2区 医学 Q1 NEUROSCIENCES
Vilém Charvát , Petra Vaculová , Blanka Železná , Lenka Maletínská , Andrea Pačesová
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引用次数: 0

摘要

厌氧性神经肽在治疗神经退行性疾病,如阿尔茨海默病(AD)方面显示出显着的潜力。其中一种强厌氧神经肽被称为可卡因和安非他明调节转录肽(CARTp),它是下丘脑中第三丰富的转录肽。之前,我们介绍了一种新的棕榈酰化的2-SS-CART类似物(61-102),这是一种具有两个二硫桥的天然CART(61-102)的特定类似物,具有厌氧和神经保护特性。本研究利用THY-Tau22转基因小鼠模型,探讨了2-SS-CART(61-102)及其棕榈酰化类似物palm-2-SS-CART(61-102)对AD Tau病理特征早期进展的影响。慢性皮下治疗CARTp类似物可改善y迷宫小鼠的短期空间记忆,减少海马CA1区神经原纤维缠结(NFT)数量,降低hy - tau22小鼠海马GFAP +星形胶质细胞水平。此外,CARTp类似物治疗显示海马突触标记物水平增加。对这些特性的有益作用使得CARTp类似物有望用于AD治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neuroprotective potential of novel CARTp analogs in the hippocampus of THY-Tau22 mouse model of Tau pathology
Anorexigenic neuropeptides have shown a remarkable potential in the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). One of the strong anorexigenic neuropeptides is called cocaine- and amphetamine-regulated transcript peptide (CARTp), which is the third most abundant transcript in the hypothalamus. Previously, we introduced a novel palmitoylated analog of 2-SS-CART(61–102), a specific analog of natural CART(61–102) with two disulfide bridges, with anorexigenic and neuroprotective properties. This study explores the impact of 2-SS-CART(61–102) and its palmitoylated analog, palm-2-SS-CART(61–102), on the early progression of Tau pathology characteristic of AD, utilizing the THY-Tau22 transgenic mouse model. Chronic subcutaneous treatment with CARTp analogs improved short-term spatial memory in the Y-maze, reduced the number of neurofibrillary tangles (NFT) in the hippocampal CA1 region, and decreased the level of GFAP + astrocytes in the hippocampus of THY-Tau22 mice. Furthermore, treatment with CARTp analogs showed increased levels of synaptic markers in the hippocampus. A beneficial effect on these attributes makes CARTp analogs promising for AD therapy.
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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