Potential neuroprotective role of transforming growth factor β1 (TGFβ1) in the brain.

TGFβ1 is a growth factor that is known to be expressed in most neurodegenerative diseases and after vascular accidents in the brain. TGFβ1 downregulates the activity of activated microglia and promotes astrogliosis. It also prevents cell death by a known mechanism dependant on astrocytes and the secretion of the plasminogen activator inhibitor 1 (PAI-1). This mechanism can provide light on what is the mechanism of action of TGFβ1 as a protective factor and it can provide the pharmacological principles in which this pathway could be used with therapeutic purposes. TGFβ1 is upregulated in most neurodegenerative diseases, however, its expression appears dramatically blocked in Huntington's disease, the fastest of those diseases in progress after the onset. This fact suggests that TGFβ1 slows down the neurodegenerative process, preventing tissue damage and neural apoptotic death. However, the exact details of TGFβ1 action are still unknown and the physiological roles on the diseases are still mysterious. Interestingly, all the data regarding the roles of TGFβ1 in health and disease have been also confirmed with the use of transgenic knockouts and TGFβ1 overexpressing mice. What possibly came as a surprise from the study of TGFβ1 overexpressing models is that combining its neuroprotective and antiproliferative effects, this cytokine generates a significant disruption in the hippocampal circuitry with its consequent learning and memory deficit.