Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Microglia

Giving out dangerous signals

Nature Reviews Neuroscience volume 9, page 327 (2008)Cite this article

The authors found that neurons isolated from mice bearing a mutation that inactivates toll-like receptor 4 (TLR4) signalling, which is known to mediate the innate immune response, were less vulnerable to cell death caused by the isolation procedure. This led them to suspect that release of an endogenous TLR4 ligand from injured neurons contributes to this cell death.

HSP60 has previously been reported to bind to TLR4 and exert a pro-inflammatory effect that is dependent on functional TLR4 signalling. Here, the authors showed that neurons release HSP60 when undergoing apoptosis or necrosis, and that both HSP60-containing supernatant from ailing neuronal cultures and recombinant HSP60 had a potent neurotoxic effect on mixed neuronal cultures (containing microglia) but not on purified neuronal cultures. Importantly, this neurotoxic effect was not observed in mixed cultures from Tlr4 mutants or when HSP60 was depleted from the supernatant (by small interfering RNA or with a monoclonal antibody), confirming that the effect was due to the action of HSP60 on microglial TLR4.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

ORIGINAL RESEARCH PAPER

  1. Lehnardt, S. et al. A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. J. Neurosci. 27, 2320–2331 (2008)

    Article  Google Scholar 

Download references

Authors
  1. Monica Hoyos Flight
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Flight, M. Giving out dangerous signals. Nat Rev Neurosci 9, 327 (2008). https://doi.org/10.1038/nrn2383

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nrn2383

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing