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

Author:
Muffat, Julien, Walker, David W., Benzer, Seymour
Source:
Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.19 pp. 7088-7093
ISSN:
0027-8424
Subject:
Alzheimer disease, Drosophila, Parkinson disease, animal injuries, apolipoprotein D, heat stress, humans, hyperoxia, imagos, lipid peroxidation, longevity, mechanism of action, mice, models, oxidative stress, paraquat, spinal cord, stress response, stress tolerance
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.
Agid:
2361385