[A potential neuroprotective and synaptic plasticity mechanism induced by estradiol through PI3K/GSK3beta in cerebral ischaemia]. / Mecanismo potencial de neuroprotección y plasticidadsináptica inducidas por el estradiol a través dePI3K/GSK3beta en la isquemia cerebra.

AIM: To review the basic molecular mechanisms that are triggered by neuroactive steroids related to protection and plasticity, and their possible therapeutic application in cases of cerebral ischaemia. DEVELOPMENT: The term 'neuroprotection' embraces a series of strategies and effects that are aimed at preventing, impeding or delaying anomalies in the functioning of the central nervous system. The neuroactive steroids, and particularly estradiol, have been widely reported owing to their neuroprotective action because they give rise to a wide range of cell signals and generate effects in genes by means of canonical pathways or through non-conventional mechanisms that are involved in neuronal survival, dendritogenesis and synapse remodelling. Thus, neuroactive steroids become an important long-term protective therapeutic alternative due to the fact that such effects converge on neuronal plasticity. CONCLUSIONS: Further work needs to be carried out to study the mechanisms of action of neuroactive steroids, especially the non-conventional ones, which involve proteins such as GSK-3beta and beta-catenin. These proteins are involved in the functions of synaptic plasticity and survival, and play a crucial role in maintaining and recovering the functional integrity of the brain after the appearance of the lesions caused by cerebral ischaemia.

Mecanismo potencial de neuroprotección y plasticidad sináptica inducidas por el estradiol a través de PI3K/GSK3beta en la isquemia cerebral / A potential neuroprotective and synaptic plasticity mechanism induced by estradioll through PI3K/GSK3beta in cerebral ischaemia

Revisar los mecanismos moleculares básicos desencadenados por esteroides neuroactivos relacionadoscon la protección y la plasticidad, y su posible aplicación terapéutica en la isquemia cerebral. Desarrollo. El término ‘neuroprotección’abarca una serie de estrategias y efectos encaminados a prevenir, impedir o retrasar anomalías en el funcionamiento del sistema nervioso central. Los esteroides neuroactivos, en particular el estradiol, se han referenciado ampliamente por su acción neuroprotectora porque originan una gran diversidad de señales celulares y producen efectos génicos por mediode rutas canónicas o a través de mecanismos no convencionales, involucrados en la supervivencia neuronal, la dendritogénesis y la remodelación sináptica, lo que convierte a los esteroides neuroactivos en una importante alternativa terapéuticade protección a largo plazo por su convergencia con dichos efectos en plasticidad neuronal. Conclusión. Es necesario profundizar en el estudio de los mecanismos de acción de los esteroides neuroactivos, en especial sobre los no convencionales, que involucran proteínas tales como la GSK-3beta y la beta-catenina, en las cuales convergen funciones de supervivencia y plasticidadsináptica y que pueden desempeñar un papel crucial en el mantenimiento y la recuperación de la integridad funcional del cerebro frente a las lesiones propias de la isquemia cerebral

To review the basic molecular mechanisms that are triggered by neuroactive steroids related to protection and plasticity, and their possible therapeutic application in cases of cerebral ischaemia. Development. The term ‘neuroprotection’ embraces a series of strategies and effects that are aimed at preventing, impeding or delaying anomalies in the functioning ofthe central nervous system. The neuroactive steroids, and particularly estradiol, have been widely reported owing to their neuroprotective action because they give rise to a wide range of cell signals and generate effects in genes by means ofcanonical pathways or through non-conventional mechanisms that are involved in neuronal survival, dendritogenesis and synapse remodelling. Thus, neuroactive steroids become an important long-term protective therapeutic alternative due to thefact that such effects converge on neuronal plasticity. Conclusions. Further work needs to be carried out to study the mechanisms of action of neuroactive steroids, especially the non-conventional ones, which involve proteins such as GSK-3beta and beta-catenin. These proteins are involved in the functions of synaptic plasticity and survival, and play a crucial role inmaintaining and recovering the functional integrity of the brain after the appearance of the lesions caused by cerebral ischaemia