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- W43033595 abstract "Neurofibromatosis-1 (NF1) is one of the most common neurogenetic diseases occurring at a frequency of 1 in 3000 worldwide and involving tumor growth and learning deficits. Neurofibromin, the product of the NF1 gene, is a tumor suppressor that regulates the adenylyl cyclase/cyclic-AMP/protein kinase A (AC/cAMP/PKA) and Ras pathways. Inactivation of the NF1 gene in both Drosophila and mice causes growth abnormalities, learning defects and early aging. Here we demonstrate that over-expression of NF1 in Drosophila significantly increases life span, improves reproductive fitness, and increases resistance to oxidative and heat stress, all mediated via AC/cAMP/PKA signaling. Over-expression of NF1 also increases electron flow through mitochondrial oxidative phosphorylation complex I, decreases mitochondrial reactive oxygen species (ROS) production, and protects mitochondrial aconitase activity. Thus, over-expression of NF1 results in increased longevity without loss of fecundity by up-regulation of cAMP production and reduced mitochondrial ROS production. The novel therapeutic strategy for NF1 disease implicated by this mechanism is currently being tested." @default.
- W43033595 created "2016-06-24" @default.
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- W43033595 date "2006-03-01" @default.
- W43033595 modified "2023-10-18" @default.
- W43033595 title "Mitority Report: Life Extension by Neurofibromatosis‐1 Over‐expression in Drosophila" @default.
- W43033595 doi "https://doi.org/10.1096/fasebj.20.4.a542-b" @default.
- W43033595 hasPublicationYear "2006" @default.
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