Autoren:	Santos Guilherme, Malena dos Stoye, Nicolai M. Rose-John, Stefan Garbers, Christoph Fellgiebel, Andreas Endres, Kristina
Titel:	The synthetic retinoid acitretin increases IL-6 in the central nervous system of Alzheimer disease model mice and human patients
Online-Publikationsdatum:	27-Jan-2020
Erscheinungsdatum:	2019
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	These days, the important role of retinoids in adult brain functionality and homeostasis is well accepted and has been proven by genomic as well as non-genomic mechanisms. In the healthy brain, numerous biological processes, e.g., cell proliferation, neurogenesis, dendritic spine formation as well as modulation of the immune system, have been attributed to retinoid signaling. This, together with the finding that retinoid metabolism is impaired in Alzheimer’s disease (AD), led to preclinical and early clinical testing of natural and synthetic retinoids as innovative pharmaceuticals with multifactorial properties. Acitretin, an aromatic retinoid, was found to exert an anti-amyloidogenic effect in mouse models for AD as well as in human patients by stimulating the alpha-secretase ADAM10. The lipophilic drug was already demonstrated to easily pass the blood brain barrier after i.p. administration and evoked increased nest building capability in the 5xFAD mouse model. Additionally, we analyzed the immune-modulatory capacity of acitretin via a multiplex array in the 5xFAD mouse model and evaluated some of our findings in human CSF derived from a pilot study using acitretin. Although several serum analytes did not display changes, Interleukin-6 (IL-6) was found to be significantly increased in both—mouse and human neural material. This demonstrates that acitretin exerts an immune stimulatory effect—besides the alpha-secretase induction—which could Impact the alleviation of learning and memory disabilities observed in the mouse model.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-25
URN:	urn:nbn:de:hebis:77-publ-595246
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Frontiers in aging neuroscience 11
Seitenzahl oder Artikelnummer:	Art. 182
Verlag:	Frontiers Research Foundation
Verlagsort:	Lausanne
Erscheinungsdatum:	2019
ISSN:	1663-4365
URL der Originalveröffentlichung:	http://dx.doi.org/10.3389/fnagi.2019.00182
DOI der Originalveröffentlichung:	10.3389/fnagi.2019.00182
Enthalten in den Sammlungen:	JGU-Publikationen