| NEUROPROTECTIVE PEPTIDES IN EXOCITOTOXICITY AND STROKE (PI: Dra M. Diaz-Guerra) |
Keywords: neuroprotection, neurodegeneration, stroke, excitotoxicity, cell-penetrating peptides, glutamate/NMDAR, BDNF/TrkB, calpain, CREB/MEF2, PSD-95
Stroke is the second cause of death worldwide and leading cause of adult disability and dementia. Pharmacological therapies for ischemic stroke (85% of cases) are still limited to thrombolytic drugs, which can be only administered to very few patients.
Cerebrovascular accidents are unpredictable and, therefore, primary death of neurons in the ischemic core cannot be avoided. However, secondary neuronal death progressively affecting the ischemic penumbra might be potentially prevented to reduce brain damage. In order to develop neuroprotective drugs for stroke therapy, we propose:
Tile image of mice cortical and sub-cortical areas showing entry of an intravenously injected biotinylated-CPP into brain
Model explaining the mechanism of action of neuroprotective peptide TFL457 which prevents excitotoxicity-induced processing of BDNF receptor TrkB-FL
To accomplish these objectives, we are using primary cultures of cortical neurons and/or astrocytes, animal models of brain ischemia and human samples from stroke patients (plasma and brain necropsias).