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Optimal exposure windows, dose scheduling, and the potential for hormetic effects or long-term consequences are poorly defined, impeding the rational design of exercise mimetic administration strategies

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Most of the compounds produced an anti-inflammatory response superior to the indomethacin control, reaching a concentration necessary for 50% inhibition of 0.45 g/ml for superoxide anion generation, and 1.68 g/ml for elastase release

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Together these results establish 4HNE as the biological ligand for GDAP1, provide mechanistic insight into 4HNE binding, and demonstrate that altered 4HNE recognition is the likely mechanism underlying CMT-causing mutants such as T157P near the 4HNE binding site