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Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch

Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the develop...

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Autores principales: Krammes, Lena, Hart, Martin, Rheinheimer, Stefanie, Diener, Caroline, Menegatti, Jennifer, Grässer, Friedrich, Keller, Andreas, Meese, Eckart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348704/
https://www.ncbi.nlm.nih.gov/pubmed/32531952
http://dx.doi.org/10.3390/cells9061442
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author Krammes, Lena
Hart, Martin
Rheinheimer, Stefanie
Diener, Caroline
Menegatti, Jennifer
Grässer, Friedrich
Keller, Andreas
Meese, Eckart
author_facet Krammes, Lena
Hart, Martin
Rheinheimer, Stefanie
Diener, Caroline
Menegatti, Jennifer
Grässer, Friedrich
Keller, Andreas
Meese, Eckart
author_sort Krammes, Lena
collection PubMed
description Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1α branch of the UPR, including the genes BIP, IRE1α, and XBP1. Upon induction of ER stress in neuronal cells, miR-34a-5p overexpression impacts the resulting UPR via a significant reduction in IRE1α and XBP1s that in turn leads to decreased viability, increased cytotoxicity and caspase activity. The possibility to modify the UPR signaling pathway by a single miRNA that targets central genes of the IRE1α branch offers new perspectives for future therapeutic approaches against neurodegeneration.
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spelling pubmed-73487042020-07-20 Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch Krammes, Lena Hart, Martin Rheinheimer, Stefanie Diener, Caroline Menegatti, Jennifer Grässer, Friedrich Keller, Andreas Meese, Eckart Cells Article Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1α branch of the UPR, including the genes BIP, IRE1α, and XBP1. Upon induction of ER stress in neuronal cells, miR-34a-5p overexpression impacts the resulting UPR via a significant reduction in IRE1α and XBP1s that in turn leads to decreased viability, increased cytotoxicity and caspase activity. The possibility to modify the UPR signaling pathway by a single miRNA that targets central genes of the IRE1α branch offers new perspectives for future therapeutic approaches against neurodegeneration. MDPI 2020-06-10 /pmc/articles/PMC7348704/ /pubmed/32531952 http://dx.doi.org/10.3390/cells9061442 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krammes, Lena
Hart, Martin
Rheinheimer, Stefanie
Diener, Caroline
Menegatti, Jennifer
Grässer, Friedrich
Keller, Andreas
Meese, Eckart
Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch
title Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch
title_full Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch
title_fullStr Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch
title_full_unstemmed Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch
title_short Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch
title_sort induction of the endoplasmic-reticulum-stress response: microrna-34a targeting of the ire1α-branch
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348704/
https://www.ncbi.nlm.nih.gov/pubmed/32531952
http://dx.doi.org/10.3390/cells9061442
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