A novel Aβ-fibrinogen interaction inhibitor rescues altered thrombosis and cognitive decline in Alzheimer's disease mice.
Bottom Line: To determine if the Aβ-fibrinogen interaction could be targeted as a potential new treatment for AD, we designed a high-throughput screen and identified RU-505 as an effective inhibitor of the Aβ-fibrinogen interaction.Furthermore, long-term treatment of RU-505 significantly reduced vascular amyloid deposition and microgliosis in the cortex and improved cognitive impairment in mouse models of AD.Our studies suggest that inhibitors targeting the Aβ-fibrinogen interaction show promise as therapy for treating AD.
Affiliation: Laboratory of Neurobiology and Genetics and High Throughput Screening Resource Center, The Rockefeller University, New York, NY 10065.Show MeSH
Related in: MedlinePlus
License 1 - License 2
Mentions: Because both AlphaLISA and the FP assay are based on optical measurements, colored compounds could significantly modify the measurement through inner filter effects. Thus, we confirmed the potency of our candidates using a pull-down assay. All five compounds showed inhibitory effects, whereas RU-505 had significant inhibitory efficacy (Fig. 2 A). These combined experiments show that the compounds identified are inhibitors of the Aβ–fibrinogen interaction.
Affiliation: Laboratory of Neurobiology and Genetics and High Throughput Screening Resource Center, The Rockefeller University, New York, NY 10065.