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In pathological conditions, astrocytes undergo significant molecular and morphological remodeling, adopting either a detrimental A1 (neurotoxic) or beneficial A2 (neuroprotective) reactive state that, respectively, drives injury progression or promotes tissue repair [132, 133]

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Furthermore, numerous signal transduction proteins (such as receptors and cytokines) also regulate the transcriptional landscape through the epigenome, resulting in the ultimate regulation of the immune response

It is possible that mutation of the iron-binding histidines changes the tertiary structure of CDO in such a way that it is no longer recognized by an ubiquitin ligase, resulting in the disruption of cysteine-sensitive ubiquitination and degradation