A Molecular Understanding of Mast Cell Activation and the Promise of Anti- Allergic Therapeutics

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Abstract:

Mast cells are central to allergic disease. Their immediate (exocytosis of granule-stored allergicmediators) and delayed (de novo synthesis of inflammatory mediators) response to an allergen underlies the symptoms seen in acute and chronic allergic disease. Thus, intervention in the allergen-mediated activation of mast cells is a long sought after goal in the treatment and management of allergic disease. The recent gain in deciphering the molecular mechanisms underlying immunoglobulin E (IgE)-mediated mast cell activation has provided optimism for the development of new therapeutic strategies. Among the most promising is the use of humanized anti-IgE antibodies that inhibit binding of IgE to its high affinity receptor (FcεRI) on the mast cell. Other strategies target molecules proximal to FcεRI, whose activities are central in mast cell activation. One such molecule, Syk kinase, has been targeted by various approaches including a small molecule inhibitor that specifically abrogates mast cell degranulation. More recently, various molecules that function to promote protein-protein interactions (adapters) were demonstrated as essential to mast cell degranulation and cytokine production. It remains to be seen if these molecules hold therapeutic promise for disease intervention. Additional studies identifying molecules required for mast cell granule fusion and content exocytosis also bodes well for discovery of new therapeutic targets. While our understanding of IgE-mediated mast cell activation is still at its inception, the modest success in identifying molecules essential to this process affords some confidence for better treatment of allergic disease.

Keywords: allergen; allergy; degranulation; ige; mast cells; molecular mechanisms; therapeutics

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867043364801

Affiliations: NIAMS/NIH, Building 10, Room 9N228, 10 Center Drive, MSC 1820, Bethesda, MD 20892-1820, USA

Publication date: August 1, 2004

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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