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Tumor Necrosis Factor-alpha and the Roles it Plays in Homeostatic and Degenerative Processes Within the Central Nervous System

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Abstract

Tumor Necrosis Factor-alpha (TNF-α) is a prototypic pro-inflammatory cytokine involved in the innate immune response. TNF-α ligation and downstream signaling with one of its cognate receptors, TNF-RI or TNF-RII, modulates fundamental processes in the brain including synapse formation and regulation, neurogenesis, regeneration, and general maintenance of the central nervous system (CNS). During states of chronic neuroinflammation, extensive experimental evidence implicates TNF-α as a key mediator in disease progression, gliosis, demyelination, inflammation, blood–brain-barrier deterioration, and cell death. This review explores the complex roles of TNF-α in the CNS under normal physiologic conditions and during neurodegeneration. We focus our discussion on Multiple Sclerosis, Parkinson’s disease, and Alzheimer’s disease, relaying the outcomes of preclinical and clinical testing of TNF-α directed therapeutic strategies, and arguing that despite the wealth of functions attributed to this central cytokine, surprisingly little is known about the cell type- and stage-specific roles of TNF-α in these debilitating disorders.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Sara L. Montgomery

  2. Departments of Neurology, University of Rochester Medical Center, Rochester, NY, 14642, USA

    William J. Bowers

  3. Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, 14642, USA

    William J. Bowers

  4. Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, 14642, USA

    William J. Bowers

  5. Center for Neural Development and Disease, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Sara L. Montgomery & William J. Bowers

  6. Department of Neurology, Center for Neural Development and Disease, University of Rochester Medical Center, 601 Elmwood Ave., Box 645, Rochester, NY, 14642, USA

    William J. Bowers

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  1. Sara L. Montgomery
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Correspondence to William J. Bowers.

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Sources of Support: This work was supported by NIH F31-AG038063 to SLM and NIH R01-AG023593 and NIH R01-AG026328 to WJB.

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Montgomery, S.L., Bowers, W.J. Tumor Necrosis Factor-alpha and the Roles it Plays in Homeostatic and Degenerative Processes Within the Central Nervous System. J Neuroimmune Pharmacol 7, 42–59 (2012). https://doi.org/10.1007/s11481-011-9287-2

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