2016
DOI: 10.1038/srep19332
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A Signaling Lipid Associated with Alzheimer’s Disease Promotes Mitochondrial Dysfunction

Abstract: 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… Show more

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Cited by 29 publications
(19 citation statements)
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“…Spare respiratory capacity is viewed as an index of mitochondrial health and is a measure of how well a cell can produce energy under stressful energy-demanding conditions [13], [34]. Notably, there is evidence that decreased spare respiratory capacity is associated with cognitive impairment in rodent models of Alzheimer disease [33]. …”
Section: Discussionmentioning
confidence: 99%
“…Spare respiratory capacity is viewed as an index of mitochondrial health and is a measure of how well a cell can produce energy under stressful energy-demanding conditions [13], [34]. Notably, there is evidence that decreased spare respiratory capacity is associated with cognitive impairment in rodent models of Alzheimer disease [33]. …”
Section: Discussionmentioning
confidence: 99%
“…It is the most common mechanism of age-related degenerative processes. Mitochondria are the primary site for ROS production, and mitochondrial dysfunction leads to the overproduction of ROS followed by ATP depletion and ultimately cell death [50,131]. The major source of ROS is the superoxide anion radicals generated by the electron transport chain during oxidative phosphorylation.…”
Section: Attenuation Of Oxidative Stressmentioning
confidence: 99%
“…On the other hand, increased cellular ceramide levels have been reported for AD. A recent study in yeast and neuronal cell culture demonstrates that treatment with platelet-activating factor, which is neurotoxic and elevated in AD, promotes mitochondrial dysfunction and ROS accumulation, accompanied by an increase of ceramide levels (Kennedy et al 2016). Enhanced ceramide levels may lead to stabilization of β-secretase and promotion of amyloidogenic cleavage of APP to Aβ (Puglielli et al 2003).…”
Section: Pathological Alterations In Cholesterol and Ceramide Metabolismmentioning
confidence: 99%