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Transforming growth factor-β

A neuroprotective factor in cerebral ischemia

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Abstract

Transforming growth factor-β (TGF-β) has diverse and multiple roles throughout the body. This review focuses on the evidence supporting its functions in the central nervous system, with a particular emphasis on its purported role in cerebral ischemia. Numerous studies have documented that TGF-β1 levels are enhanced in the brain following cerebral ischemia. As evidence that such an upregulation is beneficial, agonist studies have demonstrated that TGF-β1 reduces neuronal cell death and infarct size following middle cerebral artery occlusion (MCAO), while conversely, antagonist studies have shown increased neuronal cell death and infarct size after MCAO. These studies suggest that TGF-β1 has a neuroprotective role in cerebral ischemia. Recent work with adenoviral-mediated overexpression of TGF-β1 in vivo in mice has further implicated a neuroprotective role for TGF-β1 in cerebral ischemia, as evidenced by a reduction in neuronal cell death, infarct size, and neurological outcome. Additionally, numerous in vitro studies have documented the neuroprotective ability of TGF-β1 in neurons from a variety of species, including rats, mice, chicks, and humans. Of significant interest, TGF-β1 was shown to be protective against a wide variety of death-inducing agents/insults, including hypoxia/ischemia, glutamate excitotoxicity, β-amyloid, oxidative damage, and human immunodeficiency virus. The mechanism of TGF-β1-mediated neuroprotection remains to be resolved, but early evidence suggests that TGF-β1 regulates the expression and ratio of apoptotic (Bad) and antiapoptotic proteins (Bcl-2, Bcl-x1), creating an environment favorable for cell survival of death-inducing insults. Taken as a whole, these results suggest that TGF-β1 is an important neuroprotective factor that can reduce damage from a wide-array of death-inducing agents/insults in vitro, as well as exert protection of the brain during cerebral ischemia.

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  1. Institute of Molecular Medicine and Genetics, Department of Neurology, Program in Neurobiology, School of Medicine, Medical College of Georgia, 30912, Augusta, GA

    Krishnan M. Dhandapani & Darrell W. Brann

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  1. Krishnan M. Dhandapani
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Correspondence to Darrell W. Brann.

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The authors’ research is supported by research grants (HD-28964 and AG-17186 to DWB) from the National Institutes of Health, NICHD, and NIA.

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Dhandapani, K.M., Brann, D.W. Transforming growth factor-β. Cell Biochem Biophys 39, 13–22 (2003). https://doi.org/10.1385/CBB:39:1:13

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