L-Theanine, an amino acid in green tea, attenuates β-amyloid-induced cognitive dysfunction and neurotoxicity: Reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-κB pathways

Amyloid beta (A beta)-induced neurotoxicity is a major pathological mechanism of Alzheimer disease (AD). In this study, we investigated the inhibitory effect of L-theanine, a component of green tea (Camellia sinensis), on A beta(1-42)-induced neuronal cell death and memory impairment. Oral treatment of L-theanine (2 and 4 mg/kg) for 5 weeks in the drinking water of mice, followed by injection of A beta(1-42) (2 mu g/mouse, icv), significantly attenuated A beta(1-42)-induced memory impairment. Furthermore, L-theanine reduced A beta(1-42) levels and the accompanying A beta(1-42)-induced neuronal cell death in the cortex and hippocampus of the brain. Moreover, L-theanine inhibited A beta(1-42)-induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase as well as the activity of nuclear factor kappa B (NF-kappa B). L-Theanine also significantly reduced oxidative protein and lipid damage and the elevation of glutathione levels in the brain. These data suggest that the positive effects of L-theanine on memory may be mediated by suppression of ERK/p38 and NF-kappa B as well as the reduction of macromolecular oxidative damage. Thus, L-theanine may be useful in the prevention and treatment of AD. (C) 2009 Elsevier Inc. All rights reserved.