Journal of Neuroimmune Pharmacology

, Volume 7, Issue 1, pp 42–59

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


DOI: 10.1007/s11481-011-9287-2

Cite this article as:
Montgomery, S.L. & Bowers, W.J. J Neuroimmune Pharmacol (2012) 7: 42. doi:10.1007/s11481-011-9287-2


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.


Neuroinflammation Cytokine Development Alzheimer’s disease Parkinson’s disease Multiple Sclerosis Intracellular signaling 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineUniversity of Rochester Medical CenterRochesterUSA
  2. 2.Departments of NeurologyUniversity of Rochester Medical CenterRochesterUSA
  3. 3.Microbiology and ImmunologyUniversity of Rochester Medical CenterRochesterUSA
  4. 4.Pharmacology and PhysiologyUniversity of Rochester Medical CenterRochesterUSA
  5. 5.Center for Neural Development and DiseaseUniversity of Rochester Medical CenterRochesterUSA
  6. 6.Department of Neurology, Center for Neural Development and DiseaseUniversity of Rochester Medical CenterRochesterUSA

Personalised recommendations