One mechanism that contributes to cytochrome c detachment from IMM involves cardiolipin oxidation because oxidized cardiolipin has a much lower affinity for cytochrome c than the reduced form
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The latter is often directed towards IgG and IgE cell surface receptors
To overcome these problems, various halogenated derivatives (e.g., chlorinated or boronated PBN), alkylated derivatives having a lipophilic tail (e.g., those with dodecyl chains), bifunctional derivatives (e.g., GS-PBN, Mito-DEPMPO, 5-ChEPMPO, DECPO, and 4-HMDEPMPO), conjugates with drugs or targeting molecules (such as PEG or heparin, that both can cross the BBB), dimers, and cyclodextrin polymers have been developed in the last few years (Wang et al., 2021