Inhibition of extracellular signal-regulated kinase activity improves cognitive function in Tg2576 mice

Title
Inhibition of extracellular signal-regulated kinase activity improves cognitive function in Tg2576 mice
Author(s)
최동영Jin Peng[Jin Peng]홍진태[홍진태]
Keywords
BETA-SECRETASE ENZYME; DOUBLE-KNOCKOUT MICE; ALZHEIMERS-DISEASE; A-BETA; INDUCED APOPTOSIS; PC12 CELLS; ACTIVATION; PROTEIN; MEMORY; RAT
Issue Date
201210
Publisher
WILEY-BLACKWELL
Citation
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, v.39, no.10, pp.852 - 857
Abstract
Deposition of beta-amyloid (A beta) peptide is a defining pathological hallmark of Alzheimer's disease (AD) and is involved in memory impairment. Evidence suggests that activation of an extracellular signal-regulated kinase (ERK) pathway is related to A beta accumulation. Thus, the aim of the present study was to investigate the effects of an ERK inhibitor (U0126) on amyloidogenesis and cognitive function in Tg2576 mice. Tg2576 mice were injected with U0126 (20 mg/kg, i.p.) or vehicle (1% dimethyl sulphoxide in sterile saline) once a day for 7 days and then cognitive function was assessed by the Morris water maze test and passive avoidance test. In addition, immunostaining, western blot analysis, ELISA and enzyme activity assays were used to examine the degree of A beta deposition in the brains of Tg2576 mice. Our results showed that U0126 attenuated memory impairment and inhibited A beta deposition in the brains of Tg2576 mice. Further experiments revealed that the inhibition of A beta deposition by U0126 was due to a reduction in beta-secretase and amyloid precursor protein expression in the brains of U0126-treated Tg2576 mice. These results suggest that the ERK pathway is associated with A beta accumulation and consequent memory dysfunction in Tg2576 mice and that inhibition of the ERK pathway may be an appropriate intervention in the treatment of AD.
URI
http://hdl.handle.net/YU.REPOSITORY/27144http://dx.doi.org/10.1111/j.1440-1681.2012.12000.x
ISSN
0305-1870
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약학대학 > 약학부 > Articles
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