Frizzled receptors (FZD) belong to the superfamily of G-protein coupled receptors (GPCR). They are classified to the frizzled subfamily for which 11 members have been identified to date; FZD_1-10 and Smoothened¹. They were first identified in Drosophila melanogaster.

Like all GPCRs, Frizzled receptors have seven transmembrane domains, an extracellular N-terminus and an intracellular C-terminal tail. However, these receptors lack many features of the conventional class A, B or C GPCRs².

Activation of these receptors by WNT, leads to numerous complex signaling pathways which are generally termed β-catenin-dependent and β-catenin-independent. It is noteworthy to mention that the β-catenin-dependent pathway involves the interaction of FZD with LRP6 or LRP5 co-receptors³.

Frizzled receptors are ubiquitously expressed and play a crucial role in embryo development. They are also significantly involved in proliferation and differentiation. Indeed, dysregulation of FZD leads to various forms of cancer¹. Scientific evidence also shows their involvement in axonal remodeling and neurotransmitter release¹.

They have been associated to Alzheimer’s and Parkinson’s diseases, depression, anxiety, hypoxia and ischemia. It is thus not surprising that they have become pharmacological targets in a number of diseases and disorders.