Mutant Huntingtin promotes neuronal death through cell autonomous microglial activation via myeloid lineage- determining factors

ABSTRACT: Huntington's Disease (HD) is a fatal neurodegenerative disorder caused by an extended polyglutamine repeat in the N-terminus of the huntingtin (Htt) protein. Reactive microglia and elevated cytokine levels are observed in the brains of HD patients, but the extent to which neuroinflammation results from extrinsic or cell-autonomous mechanisms is unknown. Furthermore, the impact of microglia activation on the pathogenesis of HD remains to be established. Using genome-wide approaches, we show that expression of mutant Htt in microglia promotes cell-autonomous pro-inflammatory transcriptional activation within microglia by increasing the expression and transcriptional activities of the myeloid lineage-determining factors PU.1 and C/EBPs. Elevated levels of PU.1 and its target genes are observe

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Benner 

PROVIDER: E-GEOD-54443 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress