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

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.

Transgenerational modification of hippocampus TNF-α and S100B levels in the offspring of rats chronically exposed to morphine during adolescence

“…In pathophysiological conditions, astrocytes and especially microglia release large amounts of TNF-α (23). An increased level of TNF-α has been reported in disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis (24,25). Morphine binds to μ-opioid receptors in microglia and increases the secretion of inflammatory factors such as TNF-α (26,27).…”

The Pivotal Neuroinflammatory, Therapeutic and Neuroprotective Role of Alpha-Mangostin

“…Nevertheless, inflammatory cytokines such as interleukin (IL)-1b, IL-6, tumor necrosis factor-α (TNF)-α, reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) were elevated in cerebrospinal fluid (CSF) of PD patients. Their elevation has further influence on neurons thus the triggering of advanced neurodegeneration [30,32,33]. Studies [30,34,35] have shown that α-synuclein, the key constituent of Lewy bodies can trigger neurodegeneration in the accumulated form and partake in microglial stimulation by augmented generation of proinflammatory cytokines, thus causing an assiduous and radical nigral neurodegeneration in PD.…”

Tumor Necrosis Factor-Alpha as Biomarkers of Exposure to Indoor Pollutants Among Primary School Children in Klang Valley

“…These pro-inflammatory cytokines have been investigated mostly for their anti-inflammatory actions. TNF-α has also been suggested to have a key-role in particleinduced inflammation study ( Baune et al, 2012) and it has been concluded that TNF-α can induce an increase in airway responsiveness in healthy subjects, thus making it a cytokine candidate for the induction of airway inflammation and hyper responsiveness (Elahi et al, 2009, Montgomery andBowers, 2012). This research is intended to observe the effects of exposure to selected indoor air pollutants through the reaction of biological samples, which indicate the susceptibility of lung inflammation.…”