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First published online on May 5, 2008
This version published online on May 8, 2008
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0800896105
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PHYSIOLOGY
Human ApoD, an apolipoprotein up-regulated in neurodegenerative diseases, extends lifespan and increases stress resistance in Drosophila

Julien Muffat*,{dagger},{ddagger}, David W. Walker*,{ddagger},§, and Seymour Benzer*,¶

*Division of Biology, California Institute of Technology, Pasadena, CA 91125; and {dagger}University of Paris VI Pierre et Marie Curie, Paris 75006, France

Contributed by Seymour Benzer, March 26, 2008 (sent for review October 1, 2007)

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.

aging | Alzheimer | β-amyloid | GLaz | oxidative stress

Footnotes

Author contributions: J.M., D.W.W., and S.B. designed research; J.M. performed research; J.M. contributed new reagents/analytic tools; J.M. and D.W.W. analyzed data; and J.M., D.W.W., and S.B. wrote the paper.

§Present address: Department of Physiological Science, University of California, Los Angeles, CA 90095.

Deceased November 30, 2007.

The authors declare no conflict of interest.

{ddagger}To whom correspondence may be addressed. E-mail: julien{at}caltech.edu or davidwalker{at}ucla.edu

© 2008 by The National Academy of Sciences of the USA


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