Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer's disease mice model

Title
Anti-inflammatory and anti-amyloidogenic effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer's disease mice model
Author(s)
최동영Jin Peng[Jin Peng]김진아[김진아]이영중[이영중]정헌상[정헌상]홍진태[홍진태]
Keywords
NF-KAPPA-B; BETA-SECRETASE ENZYME; IN-VIVO MODELS; INFLAMMATORY PROCESSES; PRECURSOR PROTEIN; MEMORY IMPAIRMENT; BACE1 EXPRESSION; TRANSGENIC MICE; MOUSE MODEL; TNF-ALPHA
Issue Date
201301
Publisher
BIOMED CENTRAL LTD
Citation
JOURNAL OF NEUROINFLAMMATION, v.10
Abstract
Background: Alzheimer's disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (A beta) fibrils within the brain and activation of astrocytes and microglial cells. In this study, we examined anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl)-2-butenal (HPB242), an anti-inflammatory compound produced by the tyrosine-fructose Maillard reaction. Methods: 12-month-old Tg2576 mice were treated with HPB242 (5 mg/kg) for 1 month and then cognitive function was assessed by the Morris water maze test and passive avoidance test. In addition, western blot analysis, Gel electromobility shift assay, immunostaining,immunofluorescence staining, ELISA and enzyme activity assays were used to examine the degree of A beta deposition in the brains of Tg2576 mice. The Morris water maze task was analyzed using two-way ANOVA with repeated measures. Otherwise were analyzed by one-way ANOVA followed by Dunnett's post hoc test. Results: Treatment of HPB242 (5 mg/kg for 1 month) significantly attenuated cognitive impairments in Tg2576 transgenic mice. HPB242 also prevented amyloidogenesis in Tg2576 transgenic mice brains. This can be evidenced by A beta accumulation, BACE1, APP and C99 expression and beta-secretase activity. In addition, HPB242 suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes and microglial cells. Furthermore, activation of nuclear factor-kappaB (NF-kappa B) and signal transducer and activator of transcription 1/3 (STAT1/3) in the brain was potently inhibited by HPB242. Conclusions: Thus, these results suggest that HPB242 might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.
URI
http://hdl.handle.net/YU.REPOSITORY/26768http://dx.doi.org/10.1186/1742-2094-10-2
ISSN
1742-2094
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약학대학 > 약학부 > Articles
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