TGF-BETA-1 IS AN ORGANIZER OF RESPONSES TO NEURODEGENERATION

TGF-beta1 mRNA and protein were recently found to increase in animal brains after experimental lesions that cause local deafferentation or neuron death. Elevations of TGF-beta1 mRNA after lesions are prominent in microglia but are also observed in neurons and astrocytes. Moreover, TGF-beta1 mRNA autoinduces its own mRNA in the brain. These responses provide models for studying the increases of TGF-beta1 protein observed in betaA/amyloid-containing extracellular plaques of Alzheimer's disease (AD) and Down's syndrome (DS) and in brain cells of AIDS victims. Involvement of TGF-beta1 in these human brain disorders is discussed in relation to the potent effects of TGF-beta1 on wound healing and inflammatory responses in peripheral tissues. We hypothesize that TGF-beta1 and possibly other TGF-beta peptides have organizing roles in responses to neurodegeneration and brain injury that are similar to those observed in non-neural tissues. Work from many laboratories has shown that activities of TGF-beta peptides on brain cells include chemotaxis, modification of extracellular matrix, and regulation of cytoskeletal gene expression and of neurotrophins. Similar activities of the TGF-beta's are well established in other tissues. (C) 1993 Wiley-Liss, Inc.