The potential anti-amyloidogenic candidate, SPA1413, for Alzheimer's disease.

BACKGROUND AND PURPOSE: Recently, isoflavone derivatives have been shown to have neuroprotective effects against neurological disorders. For instance, genistein attenuated the neuroinflammation and amyloid-ß accumulation in Alzheimer's disease animal models, suggesting the potential for use to prevent and treat Alzheimer's disease. EXPERIMENTAL APPROACH: Here, 50 compounds, including isoflavone derivatives, were constructed and screened for the inhibitory effects on amyloid-ß42 fibrilization and oligomerization using the high-throughput screening formats of thioflavin T assay and multimer detection system, respectively. The potential neuroprotective effect of t3-(4-hydroxyphenyl)-2H-chromen-7-ol (SPA1413), also known as dehydroequol, idronoxil or phenoxodiol, was evaluated in cells and in 5xFAD (B6SJL) transgenic mouse, a model of Alzheimer's disease. KEY RESULTS: SPA1413 had a potent inhibitory action on both amyloid-ß fibrilization and oligomerization. In the cellular assay, SPA1413 prevented amyloid-ß-induced cytotoxicity and reduced neuroinflammation. Remarkably, the oral administration of SPA1413 ameliorated cognitive impairment, decreased amyloid-ß plaques and activated microglia in the brain of 5xFAD (B6SJL) transgenic mouse. CONCLUSION AND IMPLICATIONS: Our results strongly support the repurposing of SPA1413, which has already received fast-track status from the US Food and Drug Administration (FDA) for cancer treatment, for the treatment of Alzheimer's disease due to its potent anti-amyloidogenic and anti-neuroinflammatory actions.

Monitoring of air pollution by polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans of pine needles in Korea.

The atmospheric contamination levels of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were evaluated from the analysis of pine needles in South Korea. Pine needles were collected from 30 sampling points at five main cities in South Korea (Busan, Daegu, Gwangju, Changwon and Jeju island). The highest concentrations of PCDDs/DFs (2.19-26.88 pg I-TEQ/g of dry weight) were measured at Busan. where is the city of the highest population density and traffic volume among five cities. The lowest concentration was detected at Jeju with 0.62 pg I-TEQ/g dry weight. suggesting Jeju could be an environmental background area in Korea. The dominant homologues of PCDDs/DFs in pine needles were the lower chlorine-substituted compounds such as tetra CDDs and CDFs, and the distribution ratios of PCDDs/DFs decreased with increase of the number of chlorine substituents. Homologue profiles of pine needle samples were similar to PCDDs/DFs profiles of the vapor phase in the ambient air, and thus the pine needles absorbed the vapor phase of PCDDs/DFs from air. Results suggested that pine needles could be used as an indicator of the atmospheric contamination for PCDDs/DFs in Korea.