Iron activates microglia and directly stimulates indoleamine-2,3-dioxygenase activity in the N171-82Q mouse model of Huntington's disease.

ABSTRACT: Huntington's disease (HD) is a neurodegenerative disorder caused by a dominant CAG-repeat expansion in the huntingtin gene. Microglial activation is a key feature of HD pathology, and is present before clinical disease onset. The kynurenine pathway (KP) of tryptophan degradation is activated in HD, and is thought to contribute to disease progression. Indoleamine-2,3-dioxygenase (IDO) catalyzes the first step in this pathway; this and other pathway enzymes reside with microglia. While HD brain microglia accumulate iron, the role of iron in promoting microglial activation and KP activity is unclear. Here we utilized the neonatal iron supplementation model to investigate the relationship between iron, microglial activation and neurodegeneration in adult HD mice. We show in the N171-82Q mouse

SUBMITTER: Donley DW 

PROVIDER: S-EPMC8121302 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature