Transforming growth factor-beta signalling in brain disorders.
Transforming growth factor-beta (TGF-beta) has been characterized as an injury-related factor, based on the observation that it is strongly up-regulated in many acute or chronic central nervous system disorders. TGF-beta is generally thought to be neuroprotective and several mechanisms have been proposed to explain this beneficial action. For instance, TGF-beta protects neurons against the potentiating effect of tissue-type plasminogen activator on NMDA receptor-mediated excitotoxicity, by up-regulating type-1 plasminogen activator inhibitor expression in astrocytes. TGF-beta has also anti-apoptotic properties, through a recruitment of a mitogen-activated protein kinase pathway and a concomitant activation of anti-apoptotic members of the Bcl-2 family. These multiple mechanisms might reflect the pleiotropic nature of TGF-beta, reinforcing the potential therapeutic value of this cytokine in several central nervous system disorders.
Vivien
Denis
D
INSERM-Avenir tPA in the working brain, Centre CYCERON, Université de Caen, Bd H.Becquerel, BP 5229, 14074 Caen Cedex, France. vivien@cyceron.fr
Ali
Carine
C
D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta