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Proc Natl Acad Sci U S A. 2008 May 13;105(19):7088-93. doi: 10.1073/pnas.0800896105. Epub 2008 May 5.

Human ApoD, an apolipoprotein up-regulated in neurodegenerative diseases, extends lifespan and increases stress resistance in Drosophila.

Author information

1
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. julien@caltech.edu

Abstract

Apolipoprotein D (ApoD) expression increases in several neurological disorders and in spinal cord injury. We provide a report of a physiological role for human ApoD (hApoD): Flies overexpressing hApoD are long-lived and protected against stress conditions associated with aging and neurodegeneration, including hyperoxia, dietary paraquat, and heat stress. We show that the fly ortholog, Glial Lazarillo, is strongly up-regulated in response to these extrinsic stresses and also can protect in vitro-cultured cells in situations modeling Alzheimer's disease (AD) and Parkinson's disease (PD). In adult flies, hApoD overexpression reduces age-associated lipid peroxide accumulation, suggesting a proximal mechanism of action. Similar data obtained in the mouse [Ganfornina, M.D., et al., (2008) Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress. Aging Cell 10.1111/j.1474-9726.2008.00395.] as well as in plants (Charron et al., personal communication) suggest that ApoD and its orthologs play an evolutionarily conserved role in response to stress, possibly managing or preventing lipid peroxidation.

PMID:
18458334
PMCID:
PMC2374552
DOI:
10.1073/pnas.0800896105
[Indexed for MEDLINE]
Free PMC Article
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