TGF-beta 1 is an organizer of responses to neurodegeneration.
TGF-beta 1 mRNA and protein were recently found to increase in animal brains after experimental lesions that cause local deafferentation or neuron death. Elevations of TGF-beta 1 mRNA after lesions are prominent in microglia but are also observed in neurons and astrocytes. Moreover, TGF-beta 1 mRNA autoinduces its own mRNA in the brain. These responses provide models for studying the increases of TGF-beta 1 protein observed in beta A/amyloid-containing extracellular plaques of Alzheimer's disease (AD) and Down's syndrome (DS) and in brain cells of AIDS victims. Involvement of TGF-beta 1 in these human brain disorders is discussed in relation to the potent effects of TGF-beta 1 on wound healing and inflammatory responses in peripheral tissues. We hypothesize that TGF-beta 1 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.
Finch
C E
CE
Andrus Gerontology Center, Department of Biological Sciences, University of Southern California, Los Angeles 90089-0191.
Laping
N J
NJ
Morgan
T E
TE
Nichols
N R
NR
Pasinetti
G M
GM
D000818:Animals; D001927:Brain Diseases / Q000503:physiopathology; D006801:Humans; D007109:Immunity; D007249:Inflammation; D009410:Nerve Degeneration / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta