SDC4: A Target Enabling Package

Syndecan-4 (SDC4) is a member of a family of syndecan transmembrane receptors, which interact with a variety of extracellular targets. Syndecan signalling leads to endocytosis, endosomal sorting, and exosome export of bound ligands, a process which is dependent on the binding of syndecan-binding protein (SDCBP) to the intracellular tails of syndecans. Cellular trafficking of Aβ is dependent on syndecan/SDCBP activity (2). SDC4 was found within a TMT proteomics network module (Module 42) that contains mostly novel but also well-known AD targets, whose levels are elevated in AD patient brains (1). Inhibition of SDC4 signalling is predicted to reduce the Aβ burden in AD patient brains (3).

The aim of this TEP is to generate reagents useful for investigating the role of SDC4 in Alzheimer’s disease, such as a list of validated antibodies, generic knockout/knockdown cell lines and purified protein. Two therapeutic strategies for inhibition of SDC4 will be investigated in this TEP: 1. inhibition of SDC4 activity with an antibody and 2. inhibition of interaction of SDC4 C-terminal tail with SDCBP with small molecules.