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NitronesIn studies, nitrone-based free radical traps have shown significant potential in the treatment of neurodegenerative diseases as well as in the prolongation of life span. Initially, it was the mass action free radical trapping activity of these compounds which first brought them to the attention of the scientific community. However, research has shown that these reactions are not responsible for their therapeutic mechanistic basis of activity. Rather, the mechanism of action in the case of their neuroprotective activity seems to involve the inhibition of enhanced signal transduction processes that mediate the upregulation of genes, which produce neurotoxic products. In terms of anti aging, the most widely studied compound is the alpha-phenyl-tert-butyl-nitrone (PBN), which has been shown to extend life span in three published studies (two mouse models and one rat model). A nitrone compound called CPI-1429 has also shown ability to extend life span even though administration of the compound was begun in older animals. The downside of these studies is that it has not been shown exactly why the nitrones possess anti-aging activity. Nitrones - StudiesNitrones as neuroprotectants and antiaging drugs. Floyd RA, Hensley K, Forster MJ, Kelleher-Anderson JA, Wood PL. Ann N Y Acad Sci. 2002 Apr;959:321-9. Nitrones, their value as therapeutics and probes to understand aging. Floyd RA, Hensley K, Forster MJ, Kelleher-Andersson JA, Wood PL. Mech Ageing Dev. 2002 Apr 30;123(8):1021-31. Nitrone inhibition of age-associated oxidative damage. Floyd RA, Hensley K. Ann N Y Acad Sci. 2000;899:222-37. Protection against oxidative damage to CNS by alpha-phenyl-tert-butyl nitrone (PBN) and other spin-trapping agents: a novel series of nonlipid free radical scavengers. Carney JM, Floyd RA. J Mol Neurosci. 1991;3(1):47-57.
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