[Does transforming growth factor-beta (TGF-beta) act as a neuroprotective agent in cerebral ischemia?].
Necrosis and apoptosis are the two fundamental hallmarks of neuronal death in stroke. Nevertheless, thrombolysis, by means of the recombinant serine protease t-PA, remains until now the only approved treatment of stroke in man. Over the last years, the cytokine termed Transforming Growth Factor-beta 1 (TGF-beta 1) has been found to be strongly up regulated in the central nervous system following ischemia-induced brain damage. Recent studies have shown a neuroprotective activity of TGF-beta 1 against ischemia-induced neuronal death. In vitro, TGF-beta 1 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. Altogether, these observations suggest that either TGF-beta signaling or TGF-beta 1-modulated genes could be good targets for the development of new therapeutic strategies for stroke in man.
Docagne
Fabian
F
Université de CAEN, CNRS UMR 6551, IFR 47, Centre CYCERON, bd H. Becquerel, BP 5229, 14074 CAEN, France.
Ali
Carine
C
Lesne
Sylvain
S
Nicole
Olivier
O
MacKenzie
Eric T
ET
Buisson
Alain
A
Vivien
Denis
D
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002545:Brain Ischemia / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D018696:Neuroprotective Agents; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta