期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep19332
关键词
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资金
- Canadian Institutes of Health Research (CIHR) [MOP 311838]
- Strategic Training Initiative in Health Research (STIHR) CIHR/ Training Program in Neurodegenerative Lipidomics (CTPNL) and Institute of Aging [TGF 96121]
- CIHR Training Program in Neurodegenerative Lipidomics (CTPNL)/Institute of Aging postdoctoral fellowship
- CIHR [MOP 57810]
- Department of Molecular Biology
- NCCR in Chemical Biology, University of Geneva, Switzerland
- Canton of Geneva
- Swiss National Science Foundation
- European Research Council
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.
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