Neuroprotection by Aspirin and Sodium Salicylate Through Blockade of NF-κB Activation

Abstract

Aspirin (acetylsalicylic acid) is a commonly prescribed drug with a wide pharmacological spectrum. At concentrations compatible with amounts in plasma during chronic anti-inflammatory therapy, acetylsalicylic acid and its metabolite sodium salicylate were found to be protective against neurotoxicity elicited by the excitatory amino acid glutamate in rat primary neuronal cultures and hippocampal slices. The site of action of the drugs appeared to be downstream of glutamate receptors and to involve specific inhibition of glutamate-mediated induction of nuclear factor kappa B. These results may contribute to the emerging theme of anti-inflammatory drugs and neurodegeneration.

Additive effect between NF-κB subunits and p53 protein for transcriptional activation of human p53 promoter

“…However, one cannot rule out that these two transcription factors may also have additional or synergistic e ects in some cells or on some gene promoters. NF-kB has been shown to be required for the onset of apoptosis in a few experimental systems (Lin et al, 1995;Grilli et al, 1996;Baichwal and Baeuerle, 1997) and is required for p53-dependent apoptosis (Ryan et al, 2000).…”

Inhibitors of NF-κB signaling: 785 and counting

“…Several nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin (sodium salicylate), ibuprofen, sulindac and indomethacin, can inhibit activation of NF-kB in cell culture (Kopp and Ghosh, 1994;Grilli et al, 1996;Palayoor et al, 1998;Takada et al, 2004). Aspirin is commonly thought to act pharmacologically primarily via inhibition of prostaglandin synthesis (Weissmann, 1991).…”

Roles for NF-κB in nerve cell survival, plasticity, and disease

“…63,64 In some cases, however, support for proapoptotic functions of NF-kB has been based upon either associations between NF-kB activity and neuronal death without a causal relationship 65 or on experiments that employed drugs with multiple mechanisms of action such as aspirin and PDTC. 64,66,67 Although it is well documented that NF-kB does under certain conditions actually promote the expression of proapoptotic genes, an alternative mechanism should be considered in the complex cellular milieu of the CNS. Activation of NF-kB in glial cells (microglia and astrocytes) might indirectly promote neuronal death.…”