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

• Published in: Journal of neuroinflammation Vol. 10; no. 1; p. 2
• Main Authors: Jin, Peng, Kim, Jin-A, Choi, Dong-Young, Lee, Young-Jung, Jung, Heon Sang, Hong, Jin Tae
• Format: Journal Article
• Language: English
• Published: England BioMed Central 05-01-2013; BioMed Central Ltd; BMC
• Subjects: 2,4-bis(p-hydroxyphenyl)-2-butenal; Aldehydes - therapeutic use; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - metabolism; Amyloid precursor protein; Amyloid-beta; Amyloidogenesis; Animal models; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Astrocytes; Autoimmune diseases; beta -Site APP cleaving enzyme 1; Brain; Cognitive ability; Cricetinae; Cyclooxygenase-2; Disease Models, Animal; Enzyme-linked immunosorbent assay; Enzymes; Fibrils; Fractions; Humans; Immunofluorescence; Inflammation; Laboratory animals; Maillard reaction; Maze Learning - drug effects; Maze Learning - physiology; Memory; Mice; Mice, Transgenic; Microglial cells; Molecular modelling; Neurodegeneration; Neurodegenerative diseases; NF- Kappa B protein; NF-κB; Nitric-oxide synthase; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - metabolism; Phenols - therapeutic use; Phosphorylation; Plaque, Amyloid - drug therapy; Plaque, Amyloid - pathology; Proteins; Rodents; Stat1 protein; STAT1/3; Studies; Transcription; Transgenic mice; Western blotting
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/1742-2094-10-2

Alzheimer's disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) 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.
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 Aβ 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.
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 Aβ accumulation, BACE1, APP and C99 expression and β-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-κB) and signal transducer and activator of transcription 1/3 (STAT1/3) in the brain was potently inhibited by HPB242.
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.