Structural Synaptic Plasticity (2013)

Our research group is dedicated to three main lines of research in the field of neurodegenerative diseases.

δ The first line of research focuses on the study of the molecular mechanisms that play a part in the formation of new synapses. More specifically, we investigate the function of the membrane enzyme PI3K as it regulates the creation of new neuronal connections. Overactivation of PI3K has been shown to be capable of inducing the formation of new synapses in the nervous system in both mammals and invertebrates (Cuesto et al., 2011Martín-Peña et al., 2006). Our research group has synthesized and characterized an artificial PI3K activator, which we use as a tool for controlling synaptogenesis. When added to hippocampal neuron cultures, this activator, called PTD4-PI3KAc, induces an increase in synaptic density of nearly 30%. Based on electrophysiological recordings, these new synapses are perfectly functional and their formation is independent of new dendritic growth. Intraventricular in vivo injections increase by 30% the number of dendritic spines and also improve memory and learning (Cuesto et al., 2011).

The cognitive decline associated with Alzheimer’s disease is, to a great extent, the result of a loss in synapses. The next challenge for our group will be to demonstrate the capacity to recover lost synapses in a senile animal and, what is even more promising and exciting, in an animal model of Alzheimer.

The activating molecule has been patented, and we are currently searching for possible opportunities for collaboration in the pharmaceutical sector in order to further its development.

δ Our second line of research concerns Glaucoma. Glaucoma is a disease of the eyeball that presents as an increase in intraocular pressure. If left uncontrolled, this increase in pressure results in damage to the retinal ganglion neurons, causing irreversible blindness. Our group is researching the role of PI3K in controlling intraocular pressure and the survival of retinal ganglion neurons (Syriani et al., 2008Syriani et al., 2009).

δ The third line of research is a collaborative effort with Dr. Josep Gamez (Hospital del Valle Hebrón, Barcelona). In this study, we are identifying mutations in the genes involved in amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease. ALS is a neurodegenerative disease specifically affecting motor neurons, causing paralysis and ultimately death (Syriani et al. 2009Syriani et al. 2011Gamez et al. 2011).

δ The most recent incorporation is the collaboration with Programming and Symbolic Computation Team of university of La Rioja (Department of Mathematics and Computer Science) directed by Doctor Julio Rubio. The Project deals with the development of software for identification and quantification of neuronal structure and synaptic density.