Synaptic Dysfunction and Disease

In the Neurogenetics and Synaptopathies group we study autism and Alzheimer’s disease (AD) following approaches in Neurosciences and Human Genetics. We have identified a mutation in the synaptic gene neuroligin1 in AD, which inhibits its synaptogenic activity. These results have led to the generation of a knock-in mouse with the mutation and to its molecular and behavioral characterization.Furthermore, we study the role of neurexins as synaptic mediators of presenilins, membrane proteases mutated in familial AD (FAD).We have shown that FAD-presenilin mutations inhibit proteolytic processing of neurexins.We are currently analyzing the synaptic and behavioral defects produced by blocking this proteolytic cleavage.On the other hand, the expression of a beta-neurexin1 mutant in mice reproduces the autism-associated symptoms, which can be reversed in aged mice upon resuming the function of neurexins. We are currently characterizing the molecular mechanism responsible for the reversion