Institute of Biomedical Research of Salamanca (IBSAL)
Institute of Functional Biology and Genomics (IBFG)
Our laboratory is interested in the study of the molecular mechanisms that regulate neuronal death in excitotoxic processes (stimulation of glutamate receptors), such as cerebral ischemia (stroke), and neurodegenerative diseases (Alzheimer's disease).
Specifically, we study the role of tumor suppressor proteins, Cdh1 and p53 and related proteins, in the neurodegeneration/neurorepair balance after both acute and chronic brain injury. We also evaluate the coordination between cell cycle and neuronal differentiation and apoptosis in the adult and developing brain. Both lines connect directly with the third line of the laboratory focused on the identification of new genetic biomarkers of the functional recovery of stroke patients.
After stroke, it is essential to minimize neuronal death and promote repair mechanisms in the brain to reduce brain damage. We found that tumor suppressor proteins, especially Cdh1 and p53, play a fundamental role in the balance between brain damage and repair after cerebral ischemia. Moreover, the Arg72Pro p53 human polymorphism that regulates the proapoptotic activity of the protein, modulates the susceptibility of neurons to ischemia and conditions brain repair and functional prognosis of stroke patients. Currently, we are interested in the role of other p53-related genes, Mdm2 and Wrap53, in the susceptibility of neurons to ischemia and their possible function as genetic biomarkers of the functional recovery of stroke patients.
Rodríguez C, Ramos-Araque ME, Domínguez-Martínez M, Sobrino T, Sánchez-Morán I, Agulla J, Delgado-Esteban M, Gómez-Sánchez JC, Bolaños JP, Castillo J and Almeida A (2018) The single-nucleotide polymorphism 309T>G in the MDM2 promoter determines functional outcome after stroke Stroke 49: 2437-2444
Rodríguez C, Sobrino T, Agulla J, Bobo-Jiménez V, Ramos-Araque ME, Duarte JJ, Gómez-Sánchez JC, Bolaños JP, Castillo J and Almeida A (2017) Neovascularization and functional recovery after intracerebral hemorrhage is conditioned by the Tp53 Arg72Pro single nucleotide polymorphism Cell Death and Differentiation 24: 144-154
Bobo-Jiménez V, Delgado-Esteban M, Angibaud J, Sánchez-Morán I, de la Fuente A, Yajeya J, Nägerl UV, Castillo J, Bolaños JP and Almeida A (2017) APC/CCdh1-Rock2 pathway controls dendritic integrity and memory Proc Natl Acad Sci USA 114: 4513-4518
Delgado-Esteban M, García-Higuera I, Maestre C, Moreno S and Almeida A (2013) APC/C-Cdh1 coordinates neurogenesis and cortical size during development. Nature Communications 4: 2879
J. C. Gomez-Sanchez, M. Delgado-Esteban, I. Rodriguez-Hernandez, T. Sobrino, N. Perez de la Ossa, S. Reverte, J. P. Bolaños, R. Gonzalez-Sarmiento, J. Castillo and A. Almeida (2011) The human Tp53 Ar72Pro polymorphism explains different functional prognosis in stroke Journal of Experimental Medicine 208: 429-437