Taming Microglia in Alzheimer’s Disease: Exploring Potential Implications of Choline Alphoscerate via α7 nAChR Modulation
Anna Flavia Cantone,
Chiara Burgaletto,
Giulia Di Benedetto,
Anna Pannaccione,
Agnese Secondo,
Carlo Maria Bellanca,
Egle Augello,
Antonio Munafò,
Paola Tarro,
Renato Bernardini,
Giuseppina Cantarella
Affiliations
Anna Flavia Cantone
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Chiara Burgaletto
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Giulia Di Benedetto
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Anna Pannaccione
Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy
Agnese Secondo
Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy
Carlo Maria Bellanca
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Egle Augello
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Antonio Munafò
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Paola Tarro
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Renato Bernardini
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Giuseppina Cantarella
Section of Pharmacology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Alzheimer’s disease (AD), marked by cognitive impairment, predominantly affects the brain regions regulated by cholinergic innervation, such as the cerebral cortex and hippocampus. Cholinergic dysfunction, a key contributor to age-related cognitive decline, has spurred investigations into potential therapeutic interventions. We have previously shown that choline alphoscerate (α-GPC), a cholinergic neurotransmission-enhancing agent, protects from Aβ-mediated neurotoxicity. Herein, we investigated the effects of α-GPC on the microglial phenotype in response to Aβ via modulation of the nicotinic alpha-7 acetylcholine receptor (α7 nAChR). BV2 microglial cells were pre-treated for 1 h with α-GPC and were treated for 24, 48, and 72 h with Aβ1–42 and/or α-BTX, a selective α7nAchR antagonist. Fluorescent immunocytochemistry and Western blot analysis showed that α-GPC was able to antagonize Aβ-induced inflammatory effects. Of note, α-GPC exerted its anti-inflammatory effect by directly activating the α7nAChR receptor, as suggested by the induction of an increase in [Ca2+]i and Ach-like currents. Considering that cholinergic transmission appears crucial in regulating the inflammatory profiles of glial cells, its modulation emerges as a potential pharmaco-therapeutic target to improve outcomes in inflammatory neurodegenerative disorders, such as AD.
