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

Muffat, Julien and Walker, David W. and Benzer, Seymour (2008) Human ApoD, an apolipoprotein up-regulated in neurodegenerative diseases, extends lifespan and increases stress resistance in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 105 (19). pp. 7088-7093. ISSN 0027-8424. PMCID PMC2374552. https://resolver.caltech.edu/CaltechAUTHORS:MUFpnas08

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374552/PubMed CentralArticle
https://doi.org/10.1073/pnas.0800896105DOIUNSPECIFIED
https://doi.org/10.1073/pnas.0800896105DOIUNSPECIFIED
Additional Information:© 2008 by The National Academy of Sciences of the USA. Freely available online through the PNAS open access option. Contributed by Seymour Benzer, March 26, 2008 (received for review October 1, 2007). Published online on May 5, 2008, 10.1073/pnas.0800896105. We thank Rosalind Young, Noelle De La Rosa, and Viveca Sapin for expert technical assistance; E. A. Thomas and J. G. Sutcliffe (Scripps Research Institute, La Jolla, CA) for providing hApoD cDNA; the Murphy Laboratory for providing the gateway-modified expression vectors through the Drosophila Genetic Resource Center; Michael Reid and Carl Parker for help with cell cultures; and Diego Sanchez, Maria Ganfornina, Eric Rassart, and Fathey Sarhan for help with the article and collegial sharing of concurrent data. This work was supported by McKnight Endowment Fund for Neuroscience, Ellison Medical Foundation, National Institutes of Health, and National Science Foundation grants (to S.B.) and a Muscular Dystrophy Association development grant (to D.W.W.). J.M. is a joint Ph.D. candidate of the Biology Program at California Institute of Technology and the Brain, Cognition, and Behavior (3C) doctoral school at the University of Paris VI. J.M. and D.W.W. are forever indebted to their mentor Seymour Benzer and dedicate this article to his memory. 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. [S.B.] Deceased November 30, 2007. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/cgi/content/full/0800896105/DCSupplemental.
Funders:
Funding AgencyGrant Number
McKnight FoundationUNSPECIFIED
Ellison Medical FoundationUNSPECIFIED
NIHUNSPECIFIED
NSFUNSPECIFIED
Muscular Dystrophy AssociationUNSPECIFIED
Subject Keywords:aging; Alzheimer; β-amyloid; GLaz; oxidative stress
Issue or Number:19
PubMed Central ID:PMC2374552
Record Number:CaltechAUTHORS:MUFpnas08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:MUFpnas08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10513
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:13 May 2008
Last Modified:03 Oct 2019 00:10

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