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Divergent roles for tumor necrosis factor-alpha in the brain.

Authors
Sriram-K; O'Callaghan-JP
Source
J Neuroimmune Pharm 2007 Jun; 2(2):140-153
NIOSHTIC No.
20032592
Abstract
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)-a. Under normal physiological conditions, TNF-a 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 TNFa-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.
Keywords
Analytical-methods; Analytical-models; Analytical-processes; Analytical-Method; Pathogenicity; Pathogens; Neurological-diseases; Neuropathology; Neurotoxic-effects; Brain-disorders; Brain-tumors; Traumatic-injuries
Contact
James P. O'Callaghan, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, CDC-NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
Publication Date
20070601
Document Type
Journal Article
Email Address
jdo5@cdc.gov
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
1557-1890
NIOSH Division
HELD
Source Name
Journal of NeuroImmune Pharmacology
State
WV
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