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 due 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 MC, an allergic response may be avoided or inhibited. Compounds that attenuate the release of mediators from MCs are known as MC stabilizers. These drugs are clinically used to prevent MC effector responses towards common allergens. Although commonly prescribed clinical MC stabilizers such as disodium cromoglycate and ketotifen fumarate were used in the preventative treatment of various allergic diseases, there still remains a need of advancement towards the discovery of new MC stabilizing drugs that are able to target specific signalling molecules in order to provide better treatment option against these diseases. Among these newly discovered potential MC stabilizers, much efforts have 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 MC degranulation. Although in most cases the exact mode of action of these molecules is yet to be elucidated, all these compounds have shown MC inhibition. Therefore, they might have potential therapeutic use in the treatment of allergies and allergy related diseases where MCs are majorly involved. Thus, this mini review will focus on summarising the potential signalling molecules or receptors that have been targeted to inhibit MC degranulation, particularly those located in the upstream signalling pathway.