Huntingtin N17-Domain Phosphorylation
Is a Well-Validated Therapeutic Target

  1. The oxidation or phosphorylation status of certain N17 residues determines huntingtin localization.
  2. The Serine 16 (S16) residue is hypophosphorylated on mutant huntingtin
  3. Restoring phosphorylation or using phosphomimetics on S16 in mutant huntingtin significantly mitigates toxicity
  4. Phosphoresistant S16>A16 models show increased toxicity
  5. CK2 neo-substrates can rescue S16 phosphorylation (next slide)