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Various factors in GD can increase BBBs permeability, which allows multiple inflammatory cytokines to enter the brain and contributes to the development of neuroinflammation

Besides well-known oxidants or electrophiles, such as H 2 O 2 , 4-hydroxynonenal, and diethyl maleate (DEM), which also possess cytotoxicity, only few Nrf2 activators have been found to be useful in clinical trials (Sun et al

Thus, the exact mechanisms of L-glutamine in reducing the frequency of painful VOC is unknown and this is limiting the further development to improve the formulation for better efficacy of the agent