l-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways.
Amyloid beta (Abeta)-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 Abeta(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 Abeta(1-42) (2 microg/mouse, icv), significantly attenuated Abeta(1-42)-induced memory impairment. Furthermore, l-theanine reduced Abeta(1-42) levels and the accompanying Abeta(1-42)-induced neuronal cell death in the cortex and hippocampus of the brain. Moreover, l-theanine inhibited Abeta(1-42)-induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase as well as the activity of nuclear factor kappaB (NF-kappaB). 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-kappaB as well as the reduction of macromolecular oxidative damage. Thus, l-theanine may be useful in the prevention and treatment of AD.
Kim
Tae Il
TI
College of Pharmacy and CBITRC, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea.
Lee
Yong Kyung
YK
Park
Sang Gi
SG
Choi
Im Seop
IS
Ban
Jung Ok
JO
Park
Hyoung Kook
HK
Nam
Sang-Yoon
SY
Yun
Young Won
YW
Han
Sang Bae
SB
Oh
Ki Wan
KW
Hong
Jin Tae
JT
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D028241:Camellia sinensis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005971:Glutamates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D005978:Glutathione / Q000096:biosynthesis; D015227:Lipid Peroxidation; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016229:Amyloid beta-Peptides; D005971:Glutamates; D016328:NF-kappa B; D010446:Peptide Fragments; C026166:theanine; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione