Mechanisms of tumor necrosis factor alpha action on neurodegeneration: interaction with insulin-like growth factor-1.

Abstract

The role of cytokines and growth factors in diverse forms of neurodegeneration is now widely recognized. Several proinflammatory cytokines, notably tumor necrosis factor (TNF) α and IL-1, have been shown to mediate diverse forms of experimental neurodegeneration (1, 2), although in several cases both neurotoxic and neuroprotective actions have been reported. Similarly numerous growth factors, including insulin-like growth factor (IGF), fibroblast growth factor, transforming growth factor β, ciliary neurotrophic factor, vascular endothelial growth factor, glia-derived neurotrophic factor, brain-derived neurotrophic factor, nerve growth factor, and several neurotrophins have neuroprotective and/or neurotrophic actions in vivo and in vitro (e.g., refs. 3 and 4). The mechanisms of action of such cytokines and growth factors and their interactions between these molecules are largely unknown but are major questions in neurobiology and are of direct relevance in the search for potential treatments for neurodegenerative disease.