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Sickle cell disease: Its molecular mechanism and the one drug that treats it
Journal article   Peer reviewed

Sickle cell disease: Its molecular mechanism and the one drug that treats it

Frank A. Ferrone
International journal of biological macromolecules, v 93(Pt A), pp 1168-1173
Dec 2016
PMID: 27667542

Abstract

Assembly Hydroxyurea Nucleation
Sickle cell disease is probably the first known assembly disease, and its mechanism has been extensively studied. It arises because of the expression of a mutant hemoglobin that can polymerize, and which does so by a double nucleation mechanism that is now seen to operate in other diseases. The polymers so formed lead to circulatory obstruction in the microcirculation. The accuracy of the description that has been developed is sufficient to describe precisely the impact of molecules that cannot join polymers but that still crowd the solution, including fetal hemoglobin. The one approved drug, hydroxyurea, is thought to achieve its benefit by enhancing the production of fetal hemoglobin, but the effects of the drug on polymerization exceed what the added fetal hemoglobin can accomplish. While some possible answers to this mystery are suggested, no mechanism has been conclusively established for the remarkably efficacy of the one drug available to treat this disease.

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Web of Science research areas
Biochemistry & Molecular Biology
Chemistry, Applied
Polymer Science
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