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Overexpression of a Drosophila Homolog of Apolipoprotein D Leads to Increased Stress Resistance and Extended Lifespan

Walker, David W. and Muffat, Julien and Rundel, Colin and Benzer, Seymour (2006) Overexpression of a Drosophila Homolog of Apolipoprotein D Leads to Increased Stress Resistance and Extended Lifespan. Current Biology, 16 (7). pp. 674-9. ISSN 0960-9822.

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Increased Apolipoprotein D (ApoD) expression has been reported in various neurological disorders, including Alzheimer's disease, schizophrenia, and stroke, and in the aging brain [1]. However, whether ApoD is toxic or a defense is unknown. In a screen to identify genes that protect Drosophila against acute oxidative stress, we isolated a fly homolog of ApoD, Glial Lazarillo (GLaz). In independent transgenic lines, overexpression of GLaz resulted in increased resistance to hyperoxia (100% O_2) as well as a 29% extension of lifespan under normoxia. These flies also displayed marked improvements in climbing and walking ability after sublethal exposure to hyperoxia. Overexpression of Glaz also increased resistance to starvation without altering lipid or protein content. To determine whether GLaz might be important in protection against reperfusion injury, we subjected the flies to hypoxia, followed by recovery under normoxia. Overexpression of GLaz was protective against behavioral deficits caused in normal flies by this ischemia/reperfusion paradigm. This and the accompanying paper by Sanchez et al. [2] (in this issue of Current Biology) are the first to manipulate the levels of an ApoD homolog in a model organism. Our data suggest that human ApoD may play a protective role and thus may constitute a therapeutic target to counteract certain neurological diseases.

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Additional Information:© 2006 Elsevier. Received 6 December 2005, Revised 25 January 2006, Accepted 26 January 2006, Available online 3 April 2006. We thank Rosalind Young, John Silverlake, and Stephanie Cornelison for their expert technical assistance. J.M. is a joint Ph.D. candidate of the Biology Program at Caltech and the Brain, Cognition, and Behavior (3C) doctoral school at the University of Paris VI, funded by a Lucy Mason Clark Fellowship from Caltech and by a Glenn/AFAR scholarship for research in the Biology of Aging. D.W.W. was supported by a Wellcome Trust Prize International Traveling Research Fellowship. This research is funded by grants to S.B. from the McKnight Endowment Fund for Neuroscience, the Ellison Medical Foundation, the National Insititutes of Health, and the National Science Foundation.
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Lucy Mason Clark FellowshipUNSPECIFIED
McKnight Endowment Fund for NeuroscienceUNSPECIFIED
Ellison Medical FoundationUNSPECIFIED
Issue or Number:7
Record Number:CaltechAUTHORS:20170408-213140880
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Official Citation:David W. Walker, Julien Muffat, Colin Rundel, Seymour Benzer, Overexpression of a Drosophila Homolog of Apolipoprotein D Leads to Increased Stress Resistance and Extended Lifespan, Current Biology, Volume 16, Issue 7, 2006, Pages 674-679, ISSN 0960-9822, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76406
Deposited By: 1Science Import
Deposited On:30 Mar 2018 23:55
Last Modified:03 Oct 2019 17:00

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