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Effects of mutant huntingtin (mHtt) on cysteine metabolism. In HD (right panel), mHtt binds specificity protein 1 (SP1) and inhibits transcription of CSE. mHtt also impairs import of cystine and cysteine by the system Xc- and excitatory amino acid transporter 3 (EAAC1/EAAT3), creating an overall cysteine deficit. In addition to these effects, mHtt binds directly to CSE and inhibits its catalytic activity.
