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Donepezil modulates the endogenous immune response: implications for Alzheimer's disease.

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Title: Donepezil modulates the endogenous immune response: implications for Alzheimer's disease.
Authors: Conti, Elisa, Tremolizzo, Lucio, Santarone, Marta Elena, Tironi, Marco, Radice, Isabella, Zoia, Chiara Paola, Aliprandi, Angelo, Salmaggi, Andrea, Dominici, Roberto, Casati, Marco, Appollonio, Ildebrando, Ferrarese, Carlo
Source: Human Psychopharmacology: Clinical & Experimental. Jul2016, Vol. 31 Issue 4, p296-303. 8p.
Subjects: Donepezil, Alzheimer's disease treatment, T helper cells, Immunoprecipitation, Cholinergic receptor research, Therapeutics
Abstract: Objective Donepezil (DNPZ) is a drug commonly used for Alzheimer's disease (AD) that may favour a T helper 2 phenotype leading to increased naturally occurring auto-antibodies (NAb) against beta-amyloid (Aβ). We hypothesized the involvement of the cholinergic receptors [α7-nicotnic acetylcholine receptor (α7nAChR)] expressed on peripheral blood mononuclear cells (PBMC). Methods Fifty patients with mild-to-moderate AD, DNPZ treated (DNPZ+, n = 25) or not (DNPZ−, n = 25), and 25 matched controls were enrolled and PBMC extracted for both in vitro cultures, and real-time polymerase chain reaction and chromatin immunoprecipitation assay. Plasma samples were also obtained for Aβ and NAb determination. Results Donepezil increased in vitro the expression of the transcription factor GATA binding protein 3 (GATA3) through α7nAChR, because prevented by the specific antagonist methyllycaconitine. Ex vivo PBMC α7nAChR mRNA expression was increased in both AD groups, while GATA3 expression was not. A significant increase in the GATA3/interleukin 5 promoter association was found in DNPZ+ patients. Finally, DNPZ+ patients showed both significantly higher plasma levels of anti-Aβ NAb with respect to DNPZ− patients and Aβ 1-42 with respect to normal controls. Conclusions Donepezil might modulate a T helper 2 bias via α7nAChR leading to increased expression of NAb. Further studies on the role of the modulation of the immune response against Aβ may pave the way to innovative therapeutic strategies for AD. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
Copyright of Human Psychopharmacology: Clinical & Experimental is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Donepezil modulates the endogenous immune response: implications for Alzheimer's disease.
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  Data: <searchLink fieldCode="AR" term="%22Conti%2C+Elisa%22">Conti, Elisa</searchLink><br /><searchLink fieldCode="AR" term="%22Tremolizzo%2C+Lucio%22">Tremolizzo, Lucio</searchLink><br /><searchLink fieldCode="AR" term="%22Santarone%2C+Marta+Elena%22">Santarone, Marta Elena</searchLink><br /><searchLink fieldCode="AR" term="%22Tironi%2C+Marco%22">Tironi, Marco</searchLink><br /><searchLink fieldCode="AR" term="%22Radice%2C+Isabella%22">Radice, Isabella</searchLink><br /><searchLink fieldCode="AR" term="%22Zoia%2C+Chiara+Paola%22">Zoia, Chiara Paola</searchLink><br /><searchLink fieldCode="AR" term="%22Aliprandi%2C+Angelo%22">Aliprandi, Angelo</searchLink><br /><searchLink fieldCode="AR" term="%22Salmaggi%2C+Andrea%22">Salmaggi, Andrea</searchLink><br /><searchLink fieldCode="AR" term="%22Dominici%2C+Roberto%22">Dominici, Roberto</searchLink><br /><searchLink fieldCode="AR" term="%22Casati%2C+Marco%22">Casati, Marco</searchLink><br /><searchLink fieldCode="AR" term="%22Appollonio%2C+Ildebrando%22">Appollonio, Ildebrando</searchLink><br /><searchLink fieldCode="AR" term="%22Ferrarese%2C+Carlo%22">Ferrarese, Carlo</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Human+Psychopharmacology%3A+Clinical+%26+Experimental%22">Human Psychopharmacology: Clinical & Experimental</searchLink>. Jul2016, Vol. 31 Issue 4, p296-303. 8p.
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  Data: Objective Donepezil (DNPZ) is a drug commonly used for Alzheimer's disease (AD) that may favour a T helper 2 phenotype leading to increased naturally occurring auto-antibodies (NAb) against beta-amyloid (Aβ). We hypothesized the involvement of the cholinergic receptors [α7-nicotnic acetylcholine receptor (α7nAChR)] expressed on peripheral blood mononuclear cells (PBMC). Methods Fifty patients with mild-to-moderate AD, DNPZ treated (DNPZ+, n = 25) or not (DNPZ−, n = 25), and 25 matched controls were enrolled and PBMC extracted for both in vitro cultures, and real-time polymerase chain reaction and chromatin immunoprecipitation assay. Plasma samples were also obtained for Aβ and NAb determination. Results Donepezil increased in vitro the expression of the transcription factor GATA binding protein 3 (GATA3) through α7nAChR, because prevented by the specific antagonist methyllycaconitine. Ex vivo PBMC α7nAChR mRNA expression was increased in both AD groups, while GATA3 expression was not. A significant increase in the GATA3/interleukin 5 promoter association was found in DNPZ+ patients. Finally, DNPZ+ patients showed both significantly higher plasma levels of anti-Aβ NAb with respect to DNPZ− patients and Aβ 1-42 with respect to normal controls. Conclusions Donepezil might modulate a T helper 2 bias via α7nAChR leading to increased expression of NAb. Further studies on the role of the modulation of the immune response against Aβ may pave the way to innovative therapeutic strategies for AD. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Human Psychopharmacology: Clinical & Experimental is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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