Manuela Grimaldi1, Sara Di Marino1, Fulvio Florenzano2, Maria Teresa Ciotta3, Stefania Lucia Nori4, Manuela Rodriquez1, Giuseppe Sorrentino5,6, Anna Maria D'Ursi1, Mario Scrima1. 1. Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy. 2. Confocal Microscopy Unit, EBRI-European Brain Research Institute, Via del Fosso di Fiorano, 64, 00143 Rome, Italy. 3. Institute of Cellular Biology & Neurobiology (IBCN), CNR, IRCSS Fondazione Santa Lucia, Via del Fosso di Fiorano 64-65, 00143 Rome, Italy. 4. Department of Medicine & Surgery, University of Salerno, Via Allende, 84081 Baronissi (SA), Italy. 5. Università degli Studi di Napoli Parthenope, Napoli, Italy. 6. Istituto di Diagnosi e Cura Hermitage Capodimonte, Napoli, Italy.
Abstract
BACKGROUND: 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. CONCLUSION: 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.
BACKGROUND: 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. CONCLUSION: 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.