Transforming growth factor-beta: a neuroprotective factor in cerebral ischemia |
| |
Authors: | Dhandapani Krishnan M Brann Darrell W |
| |
Institution: | (1) Institute of Molecular Medicine and Genetics, Department of Neurology, Program in Neurobiology, School of Medicine, Medical College of Georgia, 30912 Augusta, GA |
| |
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.
The authors’ research is supported by research grants (HD-28964 and AG-17186 to DWB) from the National Institutes of Health,
NICHD, and NIA. |
| |
Keywords: | Transforming growth factor-β neuroprotection stroke ischemia excitotoxicity central nervous system brain hippocampus cerebral cortex |
本文献已被 PubMed SpringerLink 等数据库收录! |
|