TGF‐β1 is an organizer of responses to neurodgeneration

Abstract

TGF-PI mRNA and protein were recently found to increase in animal brains after experimental lesions that cause local deafferentation or neuron death. Elevations of TGF-PI mRNA after lesions are prominent in microglia but are also observed in neurons and astrocytes. Moreover, TGF-PI mRNA autoinduces its own mRNA in the brain. These responses provide models for studying the increases of TGF-PI protein observed in PAiamyloid-containing extracellular plaques of Alzheimer's disease (AD) and Down's syndrome (DS) and in brain cells of AIDS victims.Involvement of TGF-01 in these human brain disorders is discussed in relation to the potent effects of TGF-PI on wound healing and inflammatory responses in peripheral tissues.We hypothesize that TGF-PI and possibly other TGF-P 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-P peptides on brain cells include chemotaxis, modification of extracellular matrix, and regulation of cytoskeletal gene expression and of neurotrophins. Similar activities of the TGF-P's are well established in other tissues.

SMAD pathway mediation of BDNF and TGFβ2 regulation of proliferation and differentiation of hippocampal granule neurons

“…TGFβ1 and TGFβ3 have been implicated in neuroprotection, while neurotrophic functions have been ascribed to TGFβ2 and TGFβ3 (Finch et al, 1993;Böttner et al, 2000;Pratt and McPherson, 1997). The latter include stimulation (Mahanthappa and Schwarting, 1993) or inhibition (Constam et al, 1994) of neurogenesis, or both (Kane et al, 1996), as well as the regulation of neuronal differentiation (Ishihara et al, 1994;Abe et al, 1996;Cameron et al, 1998).…”

Amyloid β-Peptide Possesses a Transforming Growth Factor-β Activity

“…High molecular mass protein standards (myosin, 205 kDa; ␤-galactosidase, 116 kDa; phosphorylase, 97 kDa; bovine serum albumin, 66 kDa), A␤-(1-40), A␤-(1-16), and A␤- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were obtained from Sigma. A␤-(1-40), A␤- (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), and A␤- (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) were obtained from Bachem Bioscience, Inc. (King of Prussia, PA). Disuccinimidyl suberate was obtained from Pierce.…”

Chronic exposure to TGFβ1 regulates myeloid cell inflammatory response in an IRF7‐dependent manner

“…The TGFb subfamily includes TGFb1, TGF2, and TGF3, whose Merav Cohen et al TGFb1 impairs phenotype switch by IRF7 suppression The EMBO Journal expression is abundant in the CNS (Constam et al, 1992;Flanders et al, 1998;Wyss-Coray, 2004). TGFb1 expression by astrocytes, microglia, and neurons is up-regulated following CNS insult and is also up-regulated during aging (Finch et al, 1993). Moreover, TGFb1 is involved in mitigating inflammation, promoting resolution (Fadok et al, 1998;Wyss-Coray et al, 2001;Huynh et al, 2002;McGeachy et al, 2007), and is highly expressed relative to the other isoforms in the spinal cord following spinal cord injury (SCI) (Shechter et al, 2013).…”