Most of the neuroprotective oestrogen signalling mechanisms reviewed here have been characterized in acute models of neurodegeneration, such as experi¬mental stroke, global cerebral ischaemia or acute brain injury. The information obtained with these models may not be directly applicable to chronic neurodegenerative diseases, in which neuronal degeneration and death is a slow process accompanied by chronic neuroinflam¬mation. Further studies are necessary to determine the long-term protective signalling mechanisms of oestra¬diol in chronic neurodegenerative diseases and to ana¬lyse the neuroreparative potency of oestradiol, which has been poorly explored.