The anti-cancer drug sorafenib (Nexavar) inhibits NF-kB and may be useful in the treatment of Alzheimer’s
Key findings:
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Sorafenib (Nexavar) was found to inhibit NF-kB in the brains of mice.
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Inhibition of NF-kB was found to correlate with a reduction in COX-2 and iNOS in those same mouse brains.
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Memory was found to improve, without any change in the amyloid plaques associated with Alzheimer’s.
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A reduction in neuro-inflammation is suggested as the reason for the reduction in Alzheimer’s symptoms.
The publication:
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Neuroscience. 2009 Sep 15;162(4):1220-31. Epub 2009 May 14.
Sorafenib inhibits nuclear factor kappa B, decreases inducible nitric oxide synthase and cyclooxygenase-2 expression, and restores working memory in APPswe mice.
Echeverria V, Burgess S, Gamble-George J, Zeitlin R, Lin X, Cao C, Arendash GW.
Bay Pines VA Healthcare System, 10,000 Bay Pines Boulevard, Building 23, Room 123, Bay Pines, FL 33744, USA. Valentina.
Summary of the abstract
Alzheimer’s disease (AD) is characterized by memory loss and the upregulation of pro-neuroinflammatory factors such as cRaf-1, cyclooxygenase-2 (Cox-2), and the nuclear factor kappa B (NF-kB).
The effect of the anti-cancer drug sorafenib tosylate (Nexavar) on the expression of these factors and on cognitive performance in a mouse model of Alzheimer’s was investigated.
Sorafenib was found to inhibit cRaf-1 and NF-kB in the brains of the mice.
NF-kB controls the expression of several genes related to AD pathology, including iNOS and Cox-(2). Concurrent with NF-kB inhibition, sorafenib treatment decreased the cerebral expression of Cox-2 and iNOS in the mouse model of Alzheimer’s.
It has recently been observed that Cox-2 inhibition prevents cognitive impairment in a mouse model of AD. Consistent with the idea that Cox-2 inhibition can improve cognitive abilities, sorafenib was found to restore working memory abilities in the mouse model of Alzheimer’s without reducing Abeta levels in the brain. These findings suggest that sorafenib reduced AD pathology by reducing neuroinflammation.
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