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- Title
Taming Microglia in Alzheimer's Disease: Exploring Potential Implications of Choline Alphoscerate via α7 nAChR Modulation.
- Authors
Cantone, Anna Flavia; Burgaletto, Chiara; Di Benedetto, Giulia; Pannaccione, Anna; Secondo, Agnese; Bellanca, Carlo Maria; Augello, Egle; Munafò, Antonio; Tarro, Paola; Bernardini, Renato; Cantarella, Giuseppina
- Abstract
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.
- Subjects
ALZHEIMER'S disease; NICOTINIC acetylcholine receptors; CHOLINE; MICROGLIA; NEUROGLIA; NICOTINIC receptors
- Publication
Cells (2073-4409), 2024, Vol 13, Issue 4, p309
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells13040309