This article joins an increasing body of scientific evidence which suggests that TNF-alpha interactions with glutamate pathways may be involved in the pathogenesis of Alzheimer disease (see Zou et al., 2005 and additional references below).

TNF-amyloid interactions and other known pleotropic actions of TNF-alpha may also be involved in the pathogenesis of AD (see Rosenberg, 2005 and Tobinick et al., 2006).

References:
1. Zou JY, Crews FT. TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition. Brain Res. 2005 Feb 9;1034(1-2):11-24. Abstract

2. Taylor DL, Jones F, Kubota ES, Pocock JM. Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor alpha-induced neurotoxicity in concert with microglial-derived Fas ligand. J Neurosci. 2005 Mar 16;25(11):2952-64. Abstract

3. Pickering M, Cumiskey D, O'Connor JJ. Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp Physiol. 2005 Sep;90(5):663-70. Epub 2005 Jun 8. Review. Abstract

4. Ogoshi F, Yin HZ, Kuppumbatti Y, Song B, Amindari S, Weiss JH. Tumor necrosis-factor-alpha (TNF-alpha) induces rapid insertion of Ca2+-permeable alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels in a subset of hippocampal pyramidal neurons. Exp Neurol. 2005 Jun;193(2):384-93. Abstract

5. De A, Krueger JM, Simasko SM. Glutamate induces the expression and release of tumor necrosis factor-alpha in cultured hypothalamic cells. Brain Res. 2005 Aug 16;1053(1-2):54-61. Abstract

6. Floden AM, Li S, Combs CK. Beta-amyloid-stimulated microglia induce neuron death via synergistic stimulation of tumor necrosis factor alpha and NMDA receptors. J Neurosci. 2005 Mar 9;25(10):2566-75. Abstract

7. Leonoudakis D, Braithwaite SP, Beattie MS, Beattie EC. TNFalpha-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity? Neuron Glia Biol. 2004 Aug;1(3):263-273. Abstract

8. Rosenberg PB. Clinical aspects of inflammation in Alzheimer's disease. Int Rev Psychiatry. 2005 Dec;17(6):503-14. Review. Abstract

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