Mast Cells in Allergy: The Potential Molecular Targets in the Upstream Signalling Pathways

Abstract

Mast cells (MCs) play a crucial role in the pathogenesis of allergic diseases, attributable to their hypersensitive reaction to non-harmful substances that elicit an allergic response. As such, by interrupting certain signalling proteins within the signalling pathway of a mast cell, an allergic response may be avoided or inhibited. Compounds that attenuate the release of mediators from mast cells are known as mast cell stabilizers. These drugs are clinically applied to prevent mast cell effector responses towards common allergens. Although commonly prescribed clinical mast cell stabilizers such as disodium cromoglycate and ketotifen fumarate were applied in the preventative treatment of various allergic diseases, there remains a need of advancement of novel mast cell stabilizing drugs that can effectively target specific signalling molecules to provide better treatment option against these diseases. Among these newly discovered potential mast cell stabilizers, much effort has been given to the inhibition of vital upstream signalling molecules such as spleen tyrosine kinase, as well as surface receptors such as the high-affinity IgE receptor (FcεRI) and stem cell factor receptor (KIT). A recent study also reported that linker for activation of T cells (LAT) may also be an excellent molecular target for inhibiting mast cell degranulation. Although in most cases the exact mode of action of these molecules is yet to be elucidated, all these compounds have shown mast cell inhibition. Therefore, they might have potential therapeutic use in the treatment of allergies and allergy related diseases where mast cells are majorly involved. Thus, this mini review will focus on summarising the potential signalling molecules or receptors that have been targeted to inhibit mast cell degranulation, particularly those located in the upstream signalling pathway.