Grimaldi Manuela, Marino Sara Di, Florenzano Fulvio, Ciotta Maria Teresa, Nori Stefania Lucia, Rodriquez Manuela, Sorrentino Giuseppe, D'Ursi Anna Maria, Scrima Mario
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy.
Confocal Microscopy Unit, EBRI-European Brain Research Institute, Via del Fosso di Fiorano, 64, 00143 Rome, Italy.
Future Med Chem. 2016 Jul;8(11):1179-89. doi: 10.4155/fmc-2016-0006. Epub 2016 Jul 12.
For long time Alzheimer's disease has been attributed to a cholinergic deficit. More recently, it has been considered dependent on the accumulation of the amyloid beta peptide (Aβ), which promotes neuronal loss and impairs neuronal function. Results/methodology: In the present study, using biophysical and biochemical experiments we tested the hypothesis that in addition to its role as a neurotransmitter, acetylcholine may exert its action as an anti-Alzheimer agent through a direct interaction with Aβ.
Our data provide evidence that acetylcholine favors the soluble peptide conformation and exerts a neuroprotective effect against the neuroinflammatory and toxic effects of Aβ. The present paper paves the way toward the development of new polyfunctional anti-Alzheimer therapeutics capable of intervening on both the cholinergic transmission and the Aβ aggregation.
长期以来，阿尔茨海默病一直被认为是由胆碱能缺陷引起的。最近，人们认为它依赖于β淀粉样肽（Aβ）的积累，Aβ会促进神经元丢失并损害神经元功能。结果/方法：在本研究中，我们通过生物物理和生化实验检验了以下假设：乙酰胆碱除了作为神经递质发挥作用外，还可能通过与Aβ的直接相互作用作为抗阿尔茨海默病药物发挥作用。
我们的数据提供了证据，表明乙酰胆碱有利于可溶性肽构象，并对Aβ的神经炎症和毒性作用发挥神经保护作用。本文为开发能够干预胆碱能传递和Aβ聚集的新型多功能抗阿尔茨海默病治疗方法铺平了道路。
