Wednesday, 20th June 2018


Molecular Neuropathology

    Molecular pathways to Neurodegeneration. Cellular and Animal Models: Role of post-translational modification of Tau in its degradation by calpains.






Félix Hernández







Research summary:

--------- Fig01-300 Diagram showing how altered calcium homeostasis following NMDA receptor activation may contribute to the physiology and eventually to neuropathological activation of the calpain/GSK3/CDK5 pathway.

Calpain is one of the main proteases activated by calcium and has been implicated in Alzheimer disease. Thus, elevated cleavage and activation of calpain has been previously reported in early-stage AD suggesting that abnormalities in calcium homeostasis might be involved in the pathophysiology of the disease. In relation with tau protein, it has been demonstrated that hyperphosphorylated tau is resistance to calpain-dependent proteolysis. To study the interaction between tau, phosphorylation and calpain, we will be use transgenic mice -sulting double transgenic mice will allow us to test the synergistic contribution of both proteins in Alzheimer's disease and to study their relationship with the calpain system. In addition, we have recently described that calpain activation produces a truncation of GSK-3 which remove the inhibitory domain. We are going to study that cleavage in our transgenic models to validate GSK-3 inhibitors as pharmacological tools in Alzheimer disease.