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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4754683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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