(1192-A) AlphaLISA SureFire® Ultra™ technology as a unique platform to demonstrate TREM2/DAP12 signalling cascade activation in the neuroinflammatory disease space
Monday, February 5, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: The triggering receptor expressed on myeloid cells-2 (TREM2), a member of the immunoglobulin superfamily of receptors, is one of the hottest targets in the neuroinflammatory disease space. TREM2 signals through its association with the co-receptor DNAX-activating protein (DAP12) to trigger intracellular signal transduction. Mutations in both TREM2 and DAP12 have been associated with Nasu-Hakola disease which is characterized by dementia. At the same time, different variants of TREM2 have been linked to an increased risk for late-onset Alzheimer’s disease. Stimulation of TREM2 results in phosphorylation of tyrosine residues in the ITAM motif of DAP12 which recruits the spleen tyrosine kinase (SYK). Therefore, the study of TREM2/DAP12/SYK cascade activation results of great interest for therapeutic discovery programs.
The development of robust and sensitive assays, especially for phospho DAP12, have been challenging mainly due to the lack of specific antibodies in the market. The AlphaLISA SureFire Ultra technology constitutes a unique platform for measuring target phosphorylation and downstream cascade activation. This technology has been developed to provide exceptional assay sensitivity and enhanced signal windows for kinase screening programs.
Herein we have developed potent, rapid and homogeneous assays for measuring TREM2 activation, formation of TREM2/DAP12 complex as well as DAP12 and SYK phosphorylation. These assays in combination with the existing kits in the Surefire Ultra portfolio, provide new tools for the study of new and novel approaches to therapeutic targeting TREM2-mediated signals.