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Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo

In Alzheimer’s disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ(1–42)) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal st...

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Autores principales: Kwakowsky, Andrea, Potapov, Kyoko, Kim, SooHyun, Peppercorn, Katie, Tate, Warren P., Ábrahám, István M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754683/
https://www.ncbi.nlm.nih.gov/pubmed/26879842
http://dx.doi.org/10.1038/srep21101
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author Kwakowsky, Andrea
Potapov, Kyoko
Kim, SooHyun
Peppercorn, Katie
Tate, Warren P.
Ábrahám, István M.
author_facet Kwakowsky, Andrea
Potapov, Kyoko
Kim, SooHyun
Peppercorn, Katie
Tate, Warren P.
Ábrahám, István M.
author_sort Kwakowsky, Andrea
collection PubMed
description In Alzheimer’s disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ(1–42)) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathways has ameliorative potential without estrogenic side effects. After Aβ(1–42) injection into mouse basal forebrain, a single dose of 4-estren-3α, 17β-diol (estren), the non-classical estradiol pathway activator, restored loss of cholinergic cortical projections and also attenuated the Aβ(1–42)-induced learning deficits. Estren rapidly and directly phosphorylates c-AMP-response–element-binding-protein and extracellular-signal-regulated-kinase-1/2 in BFC neurons and restores the cholinergic fibers via estrogen receptor-α. These findings indicated that selective activation of non-classical intracellular estrogen signaling has a potential to treat the damage of cholinergic neurons in AD.
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spelling pubmed-47546832016-02-24 Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo Kwakowsky, Andrea Potapov, Kyoko Kim, SooHyun Peppercorn, Katie Tate, Warren P. Ábrahám, István M. Sci Rep Article In Alzheimer’s disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ(1–42)) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathways has ameliorative potential without estrogenic side effects. After Aβ(1–42) injection into mouse basal forebrain, a single dose of 4-estren-3α, 17β-diol (estren), the non-classical estradiol pathway activator, restored loss of cholinergic cortical projections and also attenuated the Aβ(1–42)-induced learning deficits. Estren rapidly and directly phosphorylates c-AMP-response–element-binding-protein and extracellular-signal-regulated-kinase-1/2 in BFC neurons and restores the cholinergic fibers via estrogen receptor-α. These findings indicated that selective activation of non-classical intracellular estrogen signaling has a potential to treat the damage of cholinergic neurons in AD. Nature Publishing Group 2016-02-16 /pmc/articles/PMC4754683/ /pubmed/26879842 http://dx.doi.org/10.1038/srep21101 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kwakowsky, Andrea
Potapov, Kyoko
Kim, SooHyun
Peppercorn, Katie
Tate, Warren P.
Ábrahám, István M.
Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo
title Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo
title_full Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo
title_fullStr Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo
title_full_unstemmed Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo
title_short Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo
title_sort treatment of beta amyloid 1–42 (aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754683/
https://www.ncbi.nlm.nih.gov/pubmed/26879842
http://dx.doi.org/10.1038/srep21101
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