Fig.2.

A model describing potential mechanism(s) involved in the selective vulnerability of the striatum in HD based on the YAC128 model. We propose that induction of Ido1 expression and activity in the striatum by mutant huntingtin (mHTT) and inflammation plays a central role in the observed imbalance of downstream kynurenine pathway metabolites. This imbalance, and altered transport of kynurenine pathway metabolites through the blood brain barrier (BBB) from blood to CNS, may result in increased sensitivity of striatal neurons to glutamate toxicity in HD. Dates (months) provided in the figure refer to findings at those ages of YAC128 mice, with 12 months representing an advanced stage with significant striatal cell loss.