Multiple sclerosis (MS) is an autoimmune CNS disorder characterized by axonal demyelination. T lymphocytes reactive to components of myelin basic protein proliferate and secrete cytokines underlying the neuropathology. Following demyelina-tion, 7-ketocholesterol, a major breakdown product of myelin, activates microglia to stimulate apoptosis of brain stem motor neurons . Asian populations, consuming high levels of green tea, have a lower incidence of MS .
Experimental autoimmune encephalomyelitis (EAE) is a common model of MS. Oral administration of EGCG lowered production of inflammatory lesions in the brain stem and spinal cord, and decreased relapse occurrence and development of severe disease in murine EAE . T cells from treated mice had less proliferation, and lower levels of the inflammatory cytokine tumor necrosis factor-a (TNF-a), but not interferon-y or interleukin-4, were associated with decreased activity of 20S/26S proteosomal complexes, intracellular accumulation of IKB-a, and decreased NF-kB activation.
Excitoneurotoxicity from glutamate stimulation of AMPA/kainate receptors, with the resultant rise in intracellular Ca+2 and ROS levels, contributes to neuronal death in EAE . EGCG decreases this toxicity and inhibits increased Ca+2 and ROS levels in neurons (see below).
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