Overall, these findings highlight an essential role for BDNF-TrkB signalling in the context of striatal protection and DA circuits (Fig. 7t) and offer a previously unappreciated view for future studies to determine whether pre-symptomatic changes involving the glutathione–ascorbate metabolism pathway, particularly GSTO2, occur in cell types vulnerable to neurodegenerative conditions such as HD or SCAs. The gene discussed is BDNF; the disease is Huntington disease.