A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction
| العنوان: | A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction |
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| المؤلفون: | Vanina Zaremberg, Kristin Baetz, Suriakarthiga Ganesan, Teresa M. Dunn, Mary-Ellen Harper, Linda J. Harris, Karolina Niewola-Staszkowska, Michael A. Kennedy, Kenneth Gable, Steffany A. L. Bennett, Guri Giaever, Anne Johnston, Corey Nislow, Tia C. Moffat, Robbie Loewith |
| المصدر: | Scientific Reports Scientific Reports, Vol. 6 (2016) P. 19332 |
| بيانات النشر: | Nature Publishing Group, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Candidate gene, Neurons/metabolism, TOR Serine-Threonine Kinases/metabolism, Mitochondrion, Bioinformatics, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, ddc:590, Lipid Metabolism/genetics, Multiprotein Complexes/metabolism, Cognitive decline, Alzheimer Disease/genetics/metabolism/pathology, Cells, Cultured, chemistry.chemical_classification, Membrane Potential, Mitochondrial, Neurons, Cultured, Multidisciplinary, TOR Serine-Threonine Kinases, Mitochondrial, Cell biology, Mitochondria, Signal Transduction, Ceramide, Cells, Mechanistic Target of Rapamycin Complex 2, Biology, Ceramides, Membrane Potential, Article, Cell Line, 03 medical and health sciences, Open Reading Frames, Ceramides/metabolism, Reactive Oxygen Species/metabolism, Alzheimer Disease, ddc:570, medicine, Humans, Amyloid beta-Peptides/metabolism, Mitochondria/genetics/metabolism, Reactive oxygen species, Amyloid beta-Peptides, Gene Expression Profiling, Lipid metabolism, Lipid Metabolism, Gene expression profiling, Oxidative Stress, 030104 developmental biology, chemistry, Multiprotein Complexes, Reactive Oxygen Species, 030217 neurology & neurosurgery, Oxidative stress |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6c739481d08954481a0d2194c4b79804Test http://europepmc.org/articles/PMC4725818Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6c739481d08954481a0d2194c4b79804 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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