4-O-Methylhonokiol Attenuated Memory Impairment Through Modulation of Oxidative Damage of Enzymes Involving Amyloid-beta Generation and Accumulation in a Mouse Model of Alzheimer's Disease

Title
4-O-Methylhonokiol Attenuated Memory Impairment Through Modulation of Oxidative Damage of Enzymes Involving Amyloid-beta Generation and Accumulation in a Mouse Model of Alzheimer's Disease
Author(s)
최동영최임섭[최임섭]이영중[이영중]이용경[이용경]이윤희[이윤희]김기호[김기호]김영희[김영희]전영호[전영호]김윤희[김윤희]한상배[한상배]정재경[정재경]윤여표[윤여표]오기완[오기완]황대윤[황대윤]홍진태[홍진태]
Keywords
INSULIN-DEGRADING ENZYME; TRANSGENIC MICE; PRECURSOR PROTEIN; MAGNOLIA-OFFICINALIS; NEURONAL TOXICITY; ETHANOL EXTRACT; SH-SY5Y CELLS; IN-VIVO; HONOKIOL; STRESS
Issue Date
201105
Publisher
IOS PRESS
Citation
JOURNAL OF ALZHEIMERS DISEASE, v.27, no.1, pp.127 - 141
Abstract
Accumulations of amyloid-beta (A beta) and oxidative damage are critical pathological mechanisms in the development of Alzheimer's disease (AD). We previously found that 4-O-methylhonokiol, a compound extracted from Magnolia officinalis, improved memory dysfunction in A beta-injected and presenilin 2 mutant mice through the reduction of accumulated A beta. To investigate mechanisms of the reduced A beta accumulation, we examined generation, degradation, efflux and aggregation of A beta in Swedish A beta PP AD model (A beta PPsw) mice pre-treated with 4-O-methylhonokiol (1.0 mg/kg) for 3 months. 4-O-methylhonokiol treatment recovered memory impairment and prevented neuronal cell death. This memory improving activity was associated with 4-O-methylhonokiol-induced reduction of A beta(1-42) accumulation in the brains of A beta PPsw mice. According to the reduction of A beta(1-42) accumulation, 4-O-methylhonkiol modulated oxidative damage sensitive enzymes. 4-O-methylhonkiol decreased expression and activity of brain beta-site A beta PP cleaving enzyme (BACE1), but increased clearance of A beta in the brain through an increase of expressions and activities of A beta degradation enzymes; insulin degrading enzyme and neprilysin. 4-O-methylhonkiol also increased expression of A beta transport molecule, low density lipoprotein receptor-related protein-1 in the brain and liver. 4-O-methylhonkiol decreased carbonyl protein and lipid peroxidation, but increased glutathione levels in the brains of A beta PPsw mice suggesting that oxidative damage of protein and lipid is critical in the impairment of those enzyme activities. 4-O-methylhonokiol treatment also prevented neuronal cell death in the A beta PPsw mousee brain through inactivation of caspase-3 and BAX. These results suggest that 4-O-methylhonokiol might prevent the development and progression of AD by reducing A beta accumulation through an increase of clearance and decrease of A beta generation via antioxidant mechanisms.
URI
http://hdl.handle.net/YU.REPOSITORY/25245http://dx.doi.org/10.3233/JAD-2011-110545
ISSN
1387-2877
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약학대학 > 약학부 > Articles
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