Natively Folded Chemokine (CCL28) Linked to Development of Asthma; Exploiting Unique Structural Features of CCL28 May Lead to Creation of Potent and Specific CCL28 Inhibitors

Researchers at the Medical College of Wisconsin (MCW) have linked a specific protein to the development of post-viral infection asthma, which is the first step in generating a novel type of asthma therapy designed to prevent development of post-viral asthma in young children. The findings were published in the February 13, 2015 issue of the Journal of Biological Chemistry. The article was titled “Structure-Function Analysis of CCL28 in the Development of Post-Viral Asthma. Brian F. Volkman, Ph.D., Professor of Biochemistry; and Mitchell H. Grayson, M.D., Associate Professor of Allergy and Immunology; are the lead researchers on the study. Asthma is a chronic disease of the airways that affects more than 300 million people worldwide. It is the number-one illness leading to school absences in children, and accounts for more than 1.8 million emergency room visits annually. There is no cure; all current therapies focus on providing symptomatic relief, and reducing the number and severity of attacks. "Understanding the molecular mechanisms by which asthma develops and establishes itself as a chronic disease is key to elucidating alternative and potentially curative therapies," said Dr. Grayson. The researchers had previously found evidence linking a human chemokine (protein) called CCL28 ( to the development of chronic asthma. This study is the first, however, that examines structural analysis and its impact on disease development. "We found that even in the absence of a viral infection, CCL28 can play a role in the induction of asthma pathology--when the protein is natively folded. If unfolded, it does not," explained Dr. Volkman. "We propose that by exploiting the unique structural features of CCL28, potent and specific CCL28 inhibitors may be developed.
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