Human ApoD, an apolipoprotein up-regulated in neurodegenerative diseases, extends lifespan and increases stress resistance in Drosophila.
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.
Muffat
Julien
J
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. julien@caltech.edu
Walker
David W
DW
Benzer
Seymour
S
D000375:Aging / Q000187:drug effects; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D030801:Animals, Genetically Modified; D053399:Apolipoproteins D / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008136:Longevity / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology*; D010269:Paraquat / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
C024328:APOD protein, human; D016229:Amyloid beta-Peptides; D053399:Apolipoproteins D; D002352:Carrier Proteins; D029721:Drosophila Proteins; C490457:GLaz protein, Drosophila; D006023:Glycoproteins; D008054:Lipid Peroxides; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); D010269:Paraquat