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Effects of New Galantamine Derivatives in a Scopolamine Model of Dementia in Mice
Journal of Alzheimer’s Disease ( IF 4 ) Pub Date : 2021-09-23 , DOI: 10.3233/jad-215165
Maria Lazarova 1 , Lyubka Tancheva 1 , Albena Alexandrova 1, 2 , Elina Tsvetanova 1 , Almira Georgieva 1 , Miroslava Stefanova 1 , Daniela Tsekova 3 , Lyubomir Vezenkov 3 , Reni Kalfin 1 , Diamara Uzunova 1 , Polina Petkova-Kirova 1
Affiliation  

Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by memory loss and cognitive functions decline, is a leading cause for dementia and currently ranked as the sixth foremost cause of death. As of present, treatment of AD is symptomatic without convincing therapeutic benefits and new, effective, therapeutic agents are pursued. Due to massive loss of cholinergic neurons and decreased acetylcholine levels, cholinesterase inhibitors like galantamine, remain the backbone of pharmacological treatment of the disease. In the present study, using behavioral and biochemical methods, four newly synthesized galantamine derivatives, Gal 34, Gal 43, Gal 44, and Gal 46, were evaluated for a beneficial effect in a scopolamine model of dementia in mice. They were designed to have all the advantages of galantamine and additionally to inhibit β-secretase and exert favorable effects on plasma lipids. Behavioral tests included step-through inhibitory avoidance, T-maze, and the hole-board test, whereas biochemical evaluations involved assessment of acetylcholinesterase activity, brain monoamines levels, lipid peroxidation, catalase, glutathione peroxidase, and superoxide dismutase activities along with measurement of total glutathione. Results show that Gal 43, Gal 44, and, in particular, Gal 46 are especially effective in improving both short- and long-term memory and in the case of Gal 46 having a significant effect on exploratory activity as well. Although Gal 34 did not show behavioral effects as convincing as those of the other three galantamine derivatives, it demonstrated persuasive antioxidant and restorative capacities, making all four galantamine derivatives promising AD treatment agents and prompting further research, especially that in many of our studies they performed better than galantamine.

中文翻译:

新加兰他敏衍生物对小鼠痴呆模型东莨菪碱的影响

阿尔茨海默病 (AD) 是一种以记忆丧失和认知功能下降为特征的进行性神经退行性疾病,是导致痴呆的主要原因,目前被列为第六大死因。到目前为止,AD 的治疗是对症的,没有令人信服的治疗益处,并且正在寻求新的、有效的治疗剂。由于胆碱能神经元的大量损失和乙酰胆碱水平的降低,加兰他敏等胆碱酯酶抑制剂仍然是该疾病药物治疗的支柱。在本研究中,使用行为和生化方法,评估了四种新合成的加兰他敏衍生物 Gal 34、Gal 43、Gal 44 和 Gal 46 在小鼠东莨菪碱模型中的有益作用。它们被设计成具有加兰他敏的所有优点,此外还可以抑制 β-分泌酶并对血浆脂质产生有利影响。行为测试包括逐步抑制避免、T 迷宫和孔板测试,而生化评估涉及评估乙酰胆碱酯酶活性、脑单胺水平、脂质过氧化、过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶活性以及总测量谷胱甘肽。结果表明,Gal 43、Gal 44,尤其是 Gal 46 在改善短期和长期记忆方面特别有效,并且在 Gal 46 的情况下,对探索活动也有显着影响。虽然 Gal 34 没有表现出像其他三种加兰他敏衍生物那样令人信服的行为效果,
更新日期:2021-09-24
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