Synaptic glutamate homeostasis is regulated by cystine-dependent glutamate transporters, including GLT-1 and system x<sub>c</sub><sup>-</sup> In HD, the enzyme regulating cysteine (and subsequently cystine) production, cystathionine-γ-lygase, has recently been shown to be lowered.
Although evidence is growing for an AA-glutamate interaction, several key issues require clarification: the site of action of AA on striatal neurons; the precise role of GLT1 in striatal AA release; and the mechanism by which HD interferes with this role.
The EAATs, normally expressed in both glia (EAAT1 and EAAT2) and neurons (EAAT3 and EAAT4), have previously been implicated in Huntington's disease, amyotrophic lateral sclerosis, and schizophrenia.