1. Effect of donepezil on the expression and responsiveness to LPS of CHRNA7 and CHRFAM7A in macrophages: A possible link to the cholinergic anti-inflammatory pathway.
- Author
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Maroli A, Di Lascio S, Drufuca L, Cardani S, Setten E, Locati M, Fornasari D, and Benfante R
- Subjects
- Base Sequence, Down-Regulation drug effects, Drug Synergism, Humans, Macrophages metabolism, Monocytes drug effects, Monocytes metabolism, Protein Isoforms genetics, Regulatory Sequences, Nucleic Acid, THP-1 Cells, Transcription, Genetic drug effects, alpha7 Nicotinic Acetylcholine Receptor genetics, Anti-Inflammatory Agents pharmacology, Cholinergic Agonists pharmacology, Cholinesterase Inhibitors pharmacology, Donepezil pharmacology, Gene Expression Regulation drug effects, Immunologic Factors pharmacology, Lipopolysaccharides pharmacology, Macrophages drug effects, Neuroimmunomodulation drug effects, alpha7 Nicotinic Acetylcholine Receptor biosynthesis
- Abstract
The α7 nicotinic acetylcholine receptor (CHRNA7) modulates the inflammatory response by activating the cholinergic anti-inflammatory pathway. CHRFAM7A, the human-restricted duplicated form of CHRNA7, has a negative effect on the functioning of α7 receptors, suggesting that CHRFAM7A expression regulation may be a key step in the modulation of inflammation in the human setting. The analysis of the CHRFAM7A gene's regulatory region reveals some of the mechanisms driving its expression and responsiveness to LPS in human immune cell models. Moreover, given the immunomodulatory potential of donepezil we show that it differently modulates CHRFAM7A and CHRNA7 responsiveness to LPS, thus contributing to its therapeutic potential., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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