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http://dx.doi.org/10.4062/biomolther.2014.030

Amelioration of Cognitive Dysfunction in APP/PS1 Double Transgenic Mice by Long-Term Treatment of 4-O-Methylhonokiol  

Jung, Yu-Yeon (College of Pharmacy, Chungbuk National University)
Lee, Young-Jung (School of Equine industries, Cheju Halla University)
Choi, Dong-Young (College of Pharmacy, Yeungnam University)
Hong, Jin Tae (College of Pharmacy, Chungbuk National University)
Publication Information
Biomolecules & Therapeutics / v.22, no.3, 2014 , pp. 232-238 More about this Journal
Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disease without known ways to cure. A key neuropathologic manifestation of the disease is extracellular deposition of beta-amyloid peptide (Ab). Specific mechanisms underlying the development of the disease have not yet been fully understood. In this study, we investigated effects of 4-O-methylhonokiol on memory dysfunction in APP/PS1 double transgenic mice. 4-O-methylhonokiol (1 mg/kg for 3 month) significantly reduced deficit in learning and memory of the transgenic mice, as determined by the Morris water maze test and step-through passive avoidance test. Our biochemical analysis suggested that 4-O-methylhonokiol ameliorated $A{\beta}$ accumulation in the cortex and hippocampus via reduction in beta-site APP-cleaving enzyme 1 expression. In addition, 4-O-methylhonokiol attenuated lipid peroxidation and elevated glutathione peroxidase activity in the double transgenic mice brains. Thus, suppressive effects of 4-O-methylhonokiol on $A{\beta}$ generation and oxidative stress in the brains of transgenic mice may be responsible for the enhancement in cognitive function. These results suggest that the natural compound has potential to intervene memory deficit and progressive neurodegeneration in AD patients.
Keywords
Alzheimer's disease; 4-O-methylhonokiol; APP/PS1 double transgenic; Antioxidant; Beta-site APP-cleaving enzyme;
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