Modulación de la sinapsis y su papel en patologías del sistema nervioso

Résumé

Synaptopathies are those diseases of the nervous system that occur as a result of an imbalance in the normal functioning of synapses. These abnormalities may be due to an excess in the number of synapses, as in autism spectrum disorders (ASD), or they may be by default, such as synaptic loss produced before neuronal death in neurodegenerative diseases. Thus, the study of the mechanisms that control the number of synapses and their activity is key to the development of effective therapies in a wide range of nervous system disorders of different etiology. Previously in the laboratory, the interaction of the neuronal calcium sensor NCS1 with the guanine exchange factor Ric8a was identified as a possible therapeutic target for synaptopathies. In this doctoral thesis, the use of NCS-1 /Ric8a complex stabilizing compounds has been validated in neurodegenerative models to reverse synapticdys function. I2 Imidazole receptors are widely distributed in the brain. Its selective ligands have shown that I2s are involved in analgesia, inflammation, and other aspects of human brain pathologies. Dysregulation of I2 levels is a hallmark of diseases such as glial tumors, Huntington's disease, Parkinson's disease, Alzheimer's disease, and depression among others. This work evaluates the neuroprotective role of I2 analogs at the synapse level in diseases models of different etiology, such as Alzheimer's disease or Huntington's disease...