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A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction
Fundamental changes in the composition and distribution of lipids within the brain are believed to contribute to the cognitive decline associated with Alzheimer’s disease (AD). The mechanisms by which these changes in lipid composition affect cellular function and ultimately cognition are not well u...
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/PMC4725818/ https://www.ncbi.nlm.nih.gov/pubmed/26757638 http://dx.doi.org/10.1038/srep19332 |
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author | Kennedy, Michael A. Moffat, Tia C. Gable, Kenneth Ganesan, Suriakarthiga Niewola-Staszkowska, Karolina Johnston, Anne Nislow, Corey Giaever, Guri Harris, Linda J. Loewith, Robbie Zaremberg, Vanina Harper, Mary-Ellen Dunn, Teresa Bennett, Steffany A. L. Baetz, Kristin |
author_facet | Kennedy, Michael A. Moffat, Tia C. Gable, Kenneth Ganesan, Suriakarthiga Niewola-Staszkowska, Karolina Johnston, Anne Nislow, Corey Giaever, Guri Harris, Linda J. Loewith, Robbie Zaremberg, Vanina Harper, Mary-Ellen Dunn, Teresa Bennett, Steffany A. L. Baetz, Kristin |
author_sort | Kennedy, Michael A. |
collection | PubMed |
description | Fundamental changes in the composition and distribution of lipids within the brain are believed to contribute to the cognitive decline associated with Alzheimer’s disease (AD). The mechanisms by which these changes in lipid composition affect cellular function and ultimately cognition are not well understood. Although “candidate gene” approaches can provide insight into the effects of dysregulated lipid metabolism they require a preexisting understanding of the molecular targets of individual lipid species. In this report we combine unbiased gene expression profiling with a genome-wide chemogenomic screen to identify the mitochondria as an important downstream target of PC(O-16:0/2:0), a neurotoxic lipid species elevated in AD. Further examination revealed that PC(O-16:0/2:0) similarly promotes a global increase in ceramide accumulation in human neurons which was associated with mitochondrial-derived reactive oxygen species (ROS) and toxicity. These findings suggest that PC(O-16:0/2:0)-dependent mitochondrial dysfunction may be an underlying contributing factor to the ROS production associated with AD. |
format | Online Article Text |
id | pubmed-4725818 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47258182016-01-28 A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction Kennedy, Michael A. Moffat, Tia C. Gable, Kenneth Ganesan, Suriakarthiga Niewola-Staszkowska, Karolina Johnston, Anne Nislow, Corey Giaever, Guri Harris, Linda J. Loewith, Robbie Zaremberg, Vanina Harper, Mary-Ellen Dunn, Teresa Bennett, Steffany A. L. Baetz, Kristin Sci Rep Article Fundamental changes in the composition and distribution of lipids within the brain are believed to contribute to the cognitive decline associated with Alzheimer’s disease (AD). The mechanisms by which these changes in lipid composition affect cellular function and ultimately cognition are not well understood. Although “candidate gene” approaches can provide insight into the effects of dysregulated lipid metabolism they require a preexisting understanding of the molecular targets of individual lipid species. In this report we combine unbiased gene expression profiling with a genome-wide chemogenomic screen to identify the mitochondria as an important downstream target of PC(O-16:0/2:0), a neurotoxic lipid species elevated in AD. Further examination revealed that PC(O-16:0/2:0) similarly promotes a global increase in ceramide accumulation in human neurons which was associated with mitochondrial-derived reactive oxygen species (ROS) and toxicity. These findings suggest that PC(O-16:0/2:0)-dependent mitochondrial dysfunction may be an underlying contributing factor to the ROS production associated with AD. Nature Publishing Group 2016-01-13 /pmc/articles/PMC4725818/ /pubmed/26757638 http://dx.doi.org/10.1038/srep19332 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 Kennedy, Michael A. Moffat, Tia C. Gable, Kenneth Ganesan, Suriakarthiga Niewola-Staszkowska, Karolina Johnston, Anne Nislow, Corey Giaever, Guri Harris, Linda J. Loewith, Robbie Zaremberg, Vanina Harper, Mary-Ellen Dunn, Teresa Bennett, Steffany A. L. Baetz, Kristin A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction |
title | A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction |
title_full | A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction |
title_fullStr | A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction |
title_full_unstemmed | A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction |
title_short | A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction |
title_sort | signaling lipid associated with alzheimer’s disease promotes mitochondrial dysfunction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725818/ https://www.ncbi.nlm.nih.gov/pubmed/26757638 http://dx.doi.org/10.1038/srep19332 |
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