MSN (Moesin); A Target Enabling Package

Moesin (MSN; membrane-organizing extension spike protein) contains a FERM domain (Four-point-1, Ezrin, Radixin, Moesin) that links transmembrane receptors such as CD44 to the actin cytoskeleton, in a manner regulated by phosphorylation and PIP2. A proteomic, post-mortem analysis of >400 brains identified a protein co-expression module that is highly correlated with pathological and cognitive measures of Alzheimer’s disease (AD). Moesin and CD44 have emerged as key drivers in the module. MSN is highly expressed in microglia and brain endothelium (as well as several non-brain tissues). This TEP targets the CD44-MSN interaction, to test the hypothesis that inhibiting the CD44-MSN interaction would reverse harmful activities of microglia and provide beneficial outcomes for AD patients.