Abstract
1. Necrosis and apoptosis are the two fundamental hallmarks of neuronal death in stroke. Nevertheless, thrombolysis, by using the recombinant serine protease t-PA, remains until now the only approved treatment of stroke in man.
2. Over the last years, the cytokine termed Transforming Growth Factor-β1 (TGF-β1) has been found to be strongly up-regulated in the central nervous system following ischemia-induced brain damage.
3. Recent studies have shown a neuroprotective activity of TGF-β1 against ischemia-induced neuronal death. In vitro, TGF-β1 protects neurons against excitotoxicity by inhibiting the t-PA-potentiated NMDA-induced neuronal death through a mechanism involving the up-regulation of the type-1 plasminogen activator inhibitor (PAI-1) in astrocytes.
4. In addition, TGF-β1 has been recently characterized as an antiapoptotic factor in a model of staurosporine-induced neuronal death through a mechanism involving activation of the extracellular signal-regulated kinase 1/2 (Erk1/2) and a concomitant increase phosphorylation of the antiapoptotic protein Bad.
5. Altogether, these observations suggest that either TGF-β signaling or TGF-β1-modulated genes could be good targets for the development of new therapeutic strategies for stroke in man.
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Buisson, A., Lesne, S., Docagne, F. et al. Transforming Growth Factor-β and Ischemic Brain Injury. Cell Mol Neurobiol 23, 539–550 (2003). https://doi.org/10.1023/A:1025072013107
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DOI: https://doi.org/10.1023/A:1025072013107