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

TGF-beta1 mRNA and protein were recently found to increase in animal b rains after experimental lesions that cause local deafferentation or n euron 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 response s provide models for studying the increases of TGF-beta1 protein obser ved in betaA/amyloid-containing extracellular plaques of Alzheimer's d isease (AD) and Down's syndrome (DS) and in brain cells of AIDS victim s. Involvement of TGF-beta1 in these human brain disorders is discusse d 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 re sponses to neurodegeneration and brain injury that are similar to thos e observed in non-neural tissues. Work from many laboratories has show n that activities of TGF-beta peptides on brain cells include chemotax is, modification of extracellular matrix, and regulation of cytoskelet al gene expression and of neurotrophins. Similar activities of the TGF -beta's are well established in other tissues. (C) 1993 Wiley-Liss, In c.