The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease
Open accessAbstract
Neuronal expression of familial Alzheimer's disease–mutant human amyloid precursor protein (hAPP) and hAPP-derived amyloid-β (Aβ) peptides causes synaptic dysfunction, inflammation and abnormal cerebrovascular tone in transgenic mice. Fatty acids may be involved in these processes, but their contribution to Alzheimer's disease pathogenesis is uncertain. We used a lipidomics approach to generate a broad profile of fatty acids in brain tissues of hAPP-expressing mice and found an increase in arachidonic acid and its metabolites, suggesting increased activity of the group IV isoform of phospholipase A2 (GIVA-PLA2). The levels of activated GIVA-PLA2 in the hippocampus were increased in individuals with Alzheimer's disease and in hAPP mice. Aβ caused a dose-dependent increase in GIVA-PLA2 phosphorylation in neuronal cultures. Inhibition of GIVA-PLA2 diminished Aβ-induced neurotoxicity. Genetic ablation or reduction of GIVA-PLA2 protected hAPP mice against Aβ-dependent deficits in learning and memory, behavioral alterations and premature mortality. Inhibition of GIVA-PLA2 may be beneficial in the treatment and prevention of Alzheimer's disease.
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Self-citationDistinct patterns of brain activity in young carriers of the APOE -ε4 allele
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Metadata
- Authors
- Sanchez-Mejia, R. O., Newman, J. W., Toh, S., Yu, G.-Q., Zhou, Y., Halabisky, B., Cissé, M., Scearce-Levie, K., Cheng, I. H., Gan, L., Palop, J. J., Bonventre, J. V., & Mucke, L.
- Venue
- Nature Neuroscience
- Published
- 2008-10-19
- Volume
- 11
- Issue
- 11
- Pages
- 1311-1318
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1973932627
- Cited by
- 369
- References
- 15
- FWCI
- 15.48
- Type
- journal article
- Language
- en
- Open access
- green
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- Sanchez-Mejia, R. O., Newman, J. W., Toh, S., Yu, G.-Q., Zhou, Y., Halabisky, B., Cissé, M., Scearce-Levie, K., Cheng, I. H., Gan, L., Palop, J. J., Bonventre, J. V., & Mucke, L. (2008). Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nature Neuroscience. https://doi.org/10.1038/nn.2213
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