乙酰左旋肉碱对阿尔茨海默病黑腹果蝇模型胆碱能神经元和记忆的保护作用

Olga I Bolshakova, Alexandra D Slobodina, Elizaveta E Slepneva, Svetlana V Sarantseva
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摘要

背景:阿尔茨海默病缺乏有效的治疗方法,需要寻找新的药物,并重新考虑目前在其他医学领域使用的已知物质。黑胃果蝇提供了模拟阿尔茨海默病特征、研究疾病机制和进行药物筛选的潜力。目的:研究天然低分子化合物左旋肉碱的乙酰化产物“肉碱”的神经保护作用。这种药物能够穿过血脑屏障,目前被用作改善细胞代谢的手段。方法:利用组织特异性驱动因子,在黑腹果蝇大脑特定神经元组,即多巴胺能神经元和胆碱能神经元中直接表达β淀粉样蛋白肽(42个氨基酸)。分析了乙酰左旋肉碱(肉碱)对这些神经元死亡和果蝇记忆的影响。结果:多巴胺能神经元和胆碱能神经元中淀粉样肽的表达可导致果蝇脑胆碱能神经元的神经变性和记忆障碍。将肉碱添加到动物性食品中使治疗这些疾病成为可能。同时,对多巴胺能神经元没有影响。结论:所获得的数据证实了所研究药物的神经保护作用,表明其参与了胆碱能系统的恢复,证明了使用卡尼汀治疗阿尔茨海默病的可行性。
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Acetyl-L-Carnitine Aids in Preservation of Cholinergic Neurons and Memory in the Drosophila melanogaster Model of Alzheimer's Disease.

Background: The lack of effective therapy for the treatment of Alzheimer's disease demands both the search for new drugs and the reconsideration of already known substances currently used in other areas of medicine. Drosophila melanogaster offers the potential to model features of Alzheimer's disease, study disease mechanisms, and conduct drug screening.

Objectives: The purpose of this work was to analyze the neuroprotective properties of the drug "carnicetine", which is an acetylated form of the natural low molecular weight compound L-carnitine. The drug is able to cross the blood-brain barrier and is currently used as a means of improving cellular metabolism.

Methods: Using tissue-specific drivers, direct expression of amyloid beta peptide (42 amino acids) was exhibited in certain groups of neurons in the Drosophila melanogaster brain, namely in dopaminergic and cholinergic neurons. The effect of acetyl-L-carnitine (carnicetine) on the death of these neurons and the memory of flies was analyzed.

Results: The expression of amyloid beta peptide in dopaminergic or cholinergic neurons resulted in neurodegeneration of cholinergic neurons in the Drosophila brain and memory impairment. The use of carnicetine added to animal food made it possible to treat these disorders. At the same time, no effect on dopaminergic neurons was noted.

Conclusion: The data obtained confirmed the neuroprotective properties of the drug under study, demonstrating its participation in the restoration of the cholinergic system and the feasibility of using carnicetine for the treatment of Alzheimer's disease.

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