TGF‐β1 is an organizer of responses to neurodgeneration

Abstract

TGF‐β1 mRNA and protein were recently found to increase in animal brains after experimental lesions that cause local deafferentation or neuron death. Elevations of TGF‐β1 mRNA after lesions are prominent in microglia but are also observed in neurons and astrocytes. Moreover, TGF‐β1 mRNA autoinduces its own mRNA in the brain. These responses provide models for studying the increases of TGF‐β1 protein observed in βA/amyloid‐containing extracellular plaques of Alzheimer's disease (AD) and Down's syndrome (DS) and in brain cells of AIDS victims. Involvement of TGF‐β1 in these human brain disorders is discussed in relation to the potent effects of TGF‐β1 on wound healing and inflammatory responses in peripheral tissues. We hypothesize that TGF‐β1 and possibly other TGF‐β 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‐β peptides on brain cells include chemotaxis, modification of extracellular matrix, and regulation of cytoskeletal gene expression and of neurotrophins. Similar activities of the TGF‐β's are well established in other tissues.