Cargando…
PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggest...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785689/ https://www.ncbi.nlm.nih.gov/pubmed/29153989 http://dx.doi.org/10.1016/j.stemcr.2017.10.016 |
_version_ | 1783295650991964160 |
---|---|
author | Oksanen, Minna Petersen, Andrew J. Naumenko, Nikolay Puttonen, Katja Lehtonen, Šárka Gubert Olivé, Max Shakirzyanova, Anastasia Leskelä, Stina Sarajärvi, Timo Viitanen, Matti Rinne, Juha O. Hiltunen, Mikko Haapasalo, Annakaisa Giniatullin, Rashid Tavi, Pasi Zhang, Su-Chun Kanninen, Katja M. Hämäläinen, Riikka H. Koistinaho, Jari |
author_facet | Oksanen, Minna Petersen, Andrew J. Naumenko, Nikolay Puttonen, Katja Lehtonen, Šárka Gubert Olivé, Max Shakirzyanova, Anastasia Leskelä, Stina Sarajärvi, Timo Viitanen, Matti Rinne, Juha O. Hiltunen, Mikko Haapasalo, Annakaisa Giniatullin, Rashid Tavi, Pasi Zhang, Su-Chun Kanninen, Katja M. Hämäläinen, Riikka H. Koistinaho, Jari |
author_sort | Oksanen, Minna |
collection | PubMed |
description | Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls. AD astrocytes manifest hallmarks of disease pathology, including increased β-amyloid production, altered cytokine release, and dysregulated Ca(2+) homeostasis. Furthermore, due to altered metabolism, AD astrocytes show increased oxidative stress and reduced lactate secretion, as well as compromised neuronal supportive function, as evidenced by altering Ca(2+) transients in healthy neurons. Our results reveal an important role for astrocytes in AD pathology and highlight the strength of iPSC-derived models for brain diseases. |
format | Online Article Text |
id | pubmed-5785689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-57856892018-01-29 PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease Oksanen, Minna Petersen, Andrew J. Naumenko, Nikolay Puttonen, Katja Lehtonen, Šárka Gubert Olivé, Max Shakirzyanova, Anastasia Leskelä, Stina Sarajärvi, Timo Viitanen, Matti Rinne, Juha O. Hiltunen, Mikko Haapasalo, Annakaisa Giniatullin, Rashid Tavi, Pasi Zhang, Su-Chun Kanninen, Katja M. Hämäläinen, Riikka H. Koistinaho, Jari Stem Cell Reports Article Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls. AD astrocytes manifest hallmarks of disease pathology, including increased β-amyloid production, altered cytokine release, and dysregulated Ca(2+) homeostasis. Furthermore, due to altered metabolism, AD astrocytes show increased oxidative stress and reduced lactate secretion, as well as compromised neuronal supportive function, as evidenced by altering Ca(2+) transients in healthy neurons. Our results reveal an important role for astrocytes in AD pathology and highlight the strength of iPSC-derived models for brain diseases. Elsevier 2017-11-16 /pmc/articles/PMC5785689/ /pubmed/29153989 http://dx.doi.org/10.1016/j.stemcr.2017.10.016 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Oksanen, Minna Petersen, Andrew J. Naumenko, Nikolay Puttonen, Katja Lehtonen, Šárka Gubert Olivé, Max Shakirzyanova, Anastasia Leskelä, Stina Sarajärvi, Timo Viitanen, Matti Rinne, Juha O. Hiltunen, Mikko Haapasalo, Annakaisa Giniatullin, Rashid Tavi, Pasi Zhang, Su-Chun Kanninen, Katja M. Hämäläinen, Riikka H. Koistinaho, Jari PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease |
title | PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease |
title_full | PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease |
title_fullStr | PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease |
title_full_unstemmed | PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease |
title_short | PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease |
title_sort | psen1 mutant ipsc-derived model reveals severe astrocyte pathology in alzheimer's disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785689/ https://www.ncbi.nlm.nih.gov/pubmed/29153989 http://dx.doi.org/10.1016/j.stemcr.2017.10.016 |
work_keys_str_mv | AT oksanenminna psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT petersenandrewj psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT naumenkonikolay psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT puttonenkatja psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT lehtonensarka psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT gubertolivemax psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT shakirzyanovaanastasia psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT leskelastina psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT sarajarvitimo psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT viitanenmatti psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT rinnejuhao psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT hiltunenmikko psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT haapasaloannakaisa psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT giniatullinrashid psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT tavipasi psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT zhangsuchun psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT kanninenkatjam psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT hamalainenriikkah psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease AT koistinahojari psen1mutantipscderivedmodelrevealssevereastrocytepathologyinalzheimersdisease |