Authors: Muffat J; Walker DW; Benzer S
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.Keywords: Aging/drug effects; Amyloid beta-Peptides/toxicity; Animals; Animals, Genetically Modified; Apolipoproteins D/*genetics; Carrier Proteins/genetics/metabolism; Drosophila Proteins/genetics/metabolism; Drosophila melanogaster/cytology/drug effects/*genetics; Glycoproteins/*genetics; Humans; Lipid Peroxides/metabolism; *Longevity/drug effects; Membrane Glycoproteins/genetics/metabolism; Membrane Transport Proteins/*genetics; Neurodegenerative Diseases/*genetics/*pathology; Paraquat/toxicity; Peptide Fragments/toxicity; RNA, Messenger/genetics/metabolism; Up-Regulation/drug effects/*genetics
Journal: Proceedings of the National Academy of Sciences of the United States of America
Date: May 7, 2008
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Muffat J, Walker DW, Benzer S (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: 7088-93.