Finch C E, Laping N J, Morgan T E, Nichols N R, Pasinetti G M
Andrus Gerontology Center, Department of Biological Sciences, University of Southern California, Los Angeles 90089-0191.
J Cell Biochem. 1993 Dec;53(4):314-22. doi: 10.1002/jcb.240530408.
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.
最近发现，在导致局部去传入或神经元死亡的实验性损伤后，动物大脑中的转化生长因子β1（TGF-β1）信使核糖核酸（mRNA）和蛋白质会增加。损伤后TGF-β1 mRNA的升高在小胶质细胞中很明显，但在神经元和星形胶质细胞中也能观察到。此外，TGF-β1 mRNA在大脑中能自我诱导其自身的mRNA。这些反应为研究在阿尔茨海默病（AD）和唐氏综合征（DS）含β淀粉样蛋白的细胞外斑块以及艾滋病患者脑细胞中观察到的TGF-β1蛋白增加提供了模型。本文结合TGF-β1对周围组织伤口愈合和炎症反应的强大作用，讨论了TGF-β1在这些人类脑部疾病中的作用。我们假设TGF-β1以及可能的其他TGF-β肽在对神经退行性变和脑损伤的反应中具有组织作用，这与在非神经组织中观察到的作用类似。许多实验室的研究表明，TGF-β肽对脑细胞的作用包括趋化作用、细胞外基质的修饰以及细胞骨架基因表达和神经营养因子的调节。TGF-β在其他组织中也有类似的作用，这一点已得到充分证实。
