Title: O4‐01‐03: Phenolic compounds inhibit Aβ aggregation and prevent Alzheimer pathology in <i>in vitro</i> and <i>in vivo</i> models
Abstract: Epidemiological studies have suggested that certain phenolic compounds may have preventive effects on Alzheimer's disease (AD). Inhibition of aggregation of amyloid-β protein (Aβ) is an attractive therapeutic strategy for AD. We aimed to reveal the effects of phenolic compounds on AD model mice as well as Aβ aggregation in vitro. Five phenolic compounds [curcumin (Cur), ferulic acid (FA), myricetin (Myr), nordihydroguaiaretic acid (NDGA), and rosmarinic acid (RA)] were examined for anti- Aβ aggregation effects in vitro and in vivo. In the in vitro study, we investigated the effects of the phenolic compounds on Aβ (Aβ40 and Aβ42) fibril formation, oligomerization, and destabilization of preformed fibrils by using Thioflavin T fluorescence, photo-induced cross-linking of unmodified proteins (PICUP), electron microscopy, and atomic force microscopy. In the in vivo study, AD model transgenic mice (Tg2576) were fed the phenolic compounds for 10 months from the age of 5 months, and Aβ accumulation in the brain was evaluated with immunohistochemistry and biochemical analyses. All the five phenolic compounds inhibited Aβ fibril formation and oligomerization, and destabilized preformed fibrils in vitro. In the in vivo study, immunohistochemically, Aβ deposition was significantly decreased in the brain of both the NDGA- and RA-treated groups (p < 0.05). In the RA-treated group, the level of TBS-soluble Aβ monomers was increased (p < 0.01), while that of oligomers, as probed with the A11 antibody, was decreased (p < 0.001). However, in the NDGA-treated group, the abundance of oligomers was increased (p < 0.05) without any change in the levels of TBS-soluble or TBS-insoluble Aβ. In the Cur- and Myr-treated groups, changes in the Aβ profile were similar to those in the RA-treated group, but Aβ plaque deposition was not significantly decreased. In the FA-treated group, there was no significant difference in the Aβ profile. Our results revealed that the phenolic compounds inhibited Aβ aggregation in vitro, and prevented the development of AD pathology by affecting different Aβ aggregation pathways in vivo. Clinical trials with these compounds are necessary to confirm the anti-AD effects and safety in humans.
Publication Year: 2010
Publication Date: 2010-07-01
Language: en
Type: article
Indexed In: ['crossref']
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