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Neurotoxic reactive astrocytes induce cell death via saturated lipids

Author

Listed:
  • Kevin A. Guttenplan

    (Stanford University
    Stanford University)

  • Maya K. Weigel

    (Stanford University)

  • Priya Prakash

    (Purdue University)

  • Prageeth R. Wijewardhane

    (Purdue University)

  • Philip Hasel

    (NYU School of Medicine)

  • Uriel Rufen-Blanchette

    (NYU School of Medicine)

  • Alexandra E. Münch

    (Stanford University)

  • Jacob A. Blum

    (Stanford University)

  • Jonathan Fine

    (Purdue University)

  • Mikaela C. Neal

    (University of Colorado Anschutz Medical Campus)

  • Kimberley D. Bruce

    (University of Colorado Anschutz Medical Campus)

  • Aaron D. Gitler

    (Stanford University)

  • Gaurav Chopra

    (Purdue University
    Purdue University
    Purdue University
    Purdue University)

  • Shane A. Liddelow

    (NYU School of Medicine
    NYU School of Medicine
    NYU School of Medicine
    NYU Grossman School of Medicine)

  • Ben A. Barres

    (Stanford University)

Abstract

Astrocytes regulate the response of the central nervous system to disease and injury and have been hypothesized to actively kill neurons in neurodegenerative disease1–6. Here we report an approach to isolate one component of the long-sought astrocyte-derived toxic factor5,6. Notably, instead of a protein, saturated lipids contained in APOE and APOJ lipoparticles mediate astrocyte-induced toxicity. Eliminating the formation of long-chain saturated lipids by astrocyte-specific knockout of the saturated lipid synthesis enzyme ELOVL1 mitigates astrocyte-mediated toxicity in vitro as well as in a model of acute axonal injury in vivo. These results suggest a mechanism by which astrocytes kill cells in the central nervous system.

Suggested Citation

  • Kevin A. Guttenplan & Maya K. Weigel & Priya Prakash & Prageeth R. Wijewardhane & Philip Hasel & Uriel Rufen-Blanchette & Alexandra E. Münch & Jacob A. Blum & Jonathan Fine & Mikaela C. Neal & Kimberl, 2021. "Neurotoxic reactive astrocytes induce cell death via saturated lipids," Nature, Nature, vol. 599(7883), pages 102-107, November.
    • Handle: RePEc:nat:nature:v:599:y:2021:i:7883:d:10.1038_s41586-021-03960-y
    DOI: 10.1038/s41586-021-03960-y
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    Cited by:

    1. Christina Koupourtidou & Veronika Schwarz & Hananeh Aliee & Simon Frerich & Judith Fischer-Sternjak & Riccardo Bocchi & Tatiana Simon-Ebert & Xianshu Bai & Swetlana Sirko & Frank Kirchhoff & Martin Di, 2024. "Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    2. Floriane Bretheau & Adrian Castellanos-Molina & Dominic Bélanger & Maxime Kusik & Benoit Mailhot & Ana Boisvert & Nicolas Vallières & Martine Lessard & Matthias Gunzer & Xiaoyu Liu & Éric Boilard & Ni, 2022. "The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

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