Mechanisms of NRF2 Activation to Mediate Fetal Hemoglobin Induction and Protection Against Oxidative Stress in Sickle Cell Disease

Overview

Journal Exp Biol Med (Maywood)

Specialty Biology

Date 2019 Jan 25

PMID 30674214

Citations 7

Authors

Xingguo Zhu

Aluya R Oseghale

Lopez H Nicole

Biaoru Li

Betty S Pace

Affiliations

Soon will be listed here.

Abstract

Sickle cell disease (SCD) is a group of inherited blood disorders caused by mutations in the human β-globin gene, leading to the synthesis of abnormal hemoglobin S, chronic hemolysis, and oxidative stress. Inhibition of hemoglobin S polymerization by fetal hemoglobin holds the greatest promise for treating SCD. The transcription factor NRF2, is the master regulator of the cellular oxidative stress response and activator of fetal hemoglobin expression. In animal models, various small chemical molecules activate NRF2 and ameliorate the pathophysiology of SCD. This review discusses the mechanisms of NRF2 regulation and therapeutic strategies of NRF2 activation to design the treatment options for individuals with SCD.

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