Identification of anti-inflammatory targets for Huntington's disease using a brain slice-based screening assay.


Journal Article

Huntington's disease (HD) is a late-onset, neurodegenerative disease for which there are currently no cures nor disease-modifying treatments. Here we report the identification of several potential anti-inflammatory targets for HD using an ex vivo model of HD that involves the acute transfection of human mutant huntingtin-based constructs into rat brain slices. This model recapitulates key components of the human disease, including the formation of intracellular huntingtin protein (HTT)-containing inclusions and the progressive neurodegeneration of striatal neurons-both occurring within the native tissue context of these neurons. Using this "high-throughput biology" screening platform, we conducted a hypothesis-neutral screen of a collection of drug-like compounds which identified several anti-inflammatory targets that provided neuroprotection against HTT fragment-induced neurodegeneration. The nature of these targets provide further support for non-cell autonomous mechanisms mediating significant aspects of neuropathogenesis induced by mutant HTT fragment proteins.

Full Text

Cited Authors

  • Reinhart, PH; Kaltenbach, LS; Essrich, C; Dunn, DE; Eudailey, JA; DeMarco, CT; Turmel, GJ; Whaley, JC; Wood, A; Cho, S; Lo, DC

Published Date

  • July 2011

Published In

Volume / Issue

  • 43 / 1

Start / End Page

  • 248 - 256

PubMed ID

  • 21458569

Pubmed Central ID

  • 21458569

Electronic International Standard Serial Number (EISSN)

  • 1095-953X

International Standard Serial Number (ISSN)

  • 0969-9961

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2011.03.017


  • eng