Divergent roles for tumor necrosis factor-alpha in the brain

作者：Sriram Krishnan^*; O'Callaghan James P

来源：Journal of Neuroimmune Pharmacology, 2007, 2(2): 140-153.

DOI：10.1007/s11481-007-9070-6

• brain
• brain injury
• cytokines
• microglia
• neurodegeneration
• neurotoxicity
• region specificity
• TNF-alpha
• tumor necrosis factor

Proinflammatory cytokines and chemokines have been implicated in the pathogenesis of several neurological and neurodegenerative disorders. Prominent among such factors is the pleiotropic cytokine, tumor necrosis factor (TNF)-alpha. Under normal physiological conditions, TNF-alpha orchestrates a diverse array of functions involved in immune surveillance and defense, cellular homeostasis, and protection against certain neurological insults. However, paradoxical effects of this cytokine have been observed. TNF-a is elicited in the brain following injury (ischemia, trauma), infection (HIV, meningitis), neurodegeneration (Alzheimer's, Parkinson's), and chemically induced neurotoxicity. The multifarious identity for this cytokine appears to be influenced by several mechanisms. Among the most prominent are the regulation of TNF alpha-induced NF-KB activation by adapter proteins such as TRADD and TRAF, and second, the heterogeneity of microglia and their distribution pattern across brain regions. Here, we review the differential role of TNF-a in response to brain injury, with emphasis on neurodegeneration, and discuss the possible mechanisms for such diverse and region-specific effects.

• 出版日期2007-6