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Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in central nervous system inflammation

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Abstract

In a wide variety of acute and chronic central nervous system (CNS) disorders, inflammatory processes contribute to the damage of brain cells and progression of the disease. Along with other regulatory cytokines, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is involved in the pathology of multiple sclerosis (MS) and murine experimental autoimmune encephalomyelitis (EAE), bacterial meningitis (BM), HIV encephalitis (HIVE), stroke and Alzheimer's disease (AD). In these conditions, TRAIL is released within the brain mainly by activated microglia and leukocytes infiltrating from the blood stream. TRAIL promotes apoptosis of parenchymal cells in MS/EAE, HIVE, AD and stroke through interaction with TRAIL death receptors expressed on these cells. Frequently, cells in the diseased brain display increased susceptibility to apoptosis induction by TRAIL due to upregulation of death receptors and downregulation of decoy receptors. On the other hand, TRAIL inhibits the proliferation of encephalitogenic T cells in EAE, and it is involved in the clearance of infected brain macrophages in HIVE and of activated neutrophils in BM by interaction with their death receptors. Especially in BM, the ability of TRAIL to limit an acute granulocyte-driven inflammation carries significant neuroprotective potential. Given the diversity of beneficial and harmful effects in the immune and nervous system, TRAIL is a double-edged sword in diseases involving CNS inflammation.

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Acknowledgements

This work was supported by a grant of Wilhelm Sander Stiftung to O.H. and by grants of Deutsche Forschungsgemeinschaft (DFG) to F.Z. and J.R.W.

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurology, Charité—Universitätsmedizin Berlin, Berlin, Germany

    Olaf Hoffmann

  2. Cecilie Vogt Clinic for Neurology, Charité—Universitätsmedizin Berlin, Berlin, Germany

    Frauke Zipp

  3. Department of Cell Biology and Neurobiology, Charité—Universitätsmedizin Berlin, Berlin, Germany

    Joerg R. Weber

Authors
  1. Olaf Hoffmann
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  2. Frauke Zipp
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  3. Joerg R. Weber
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Corresponding author

Correspondence to Joerg R. Weber.

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Hoffmann, O., Zipp, F. & Weber, J.R. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in central nervous system inflammation. J Mol Med 87, 753–763 (2009). https://doi.org/10.1007/s00109-009-0484-x

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  • DOI: https://doi.org/10.1007/s00109-009-0484-x

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