Screening of chemical compounds to restore the defective trafficking of R451C Neuroligin3
| Componente | Categoria |
|---|---|
| Antonella De Jaco | Tutor di riferimento |
Autism Spectrum Disorders (ASDs) are neurodevelopmental syndromes, characterized by behavioral deficits and a strong genetic background.
In the last decades, several autism-linked mutations have been found in the Neuroligins (NLGNs) family of proteins. Between these mutations, the R451C substitution in NLGN3 has been highly characterized. It is known from in vitro studies, that the R451C mutation affects the folding of the extracellular domain of the protein, causing its retention in the Endoplasmic Reticulum (ER). It is estimated that only 10% of the mutant protein can reach the synapse and it has been shown, both in vitro and in vivo, that the loss of NLGN3 on the cell surface causes alterations in synaptic functions in several brain regions.
We have generated and characterized a new cell-based model system that allow us to study protein trafficking and its modulation by chemical compounds with chaperone-like activity.
The aim of this project is to screen a library of compounds approved by the American Food and Drug Administration with the aim to restore normal trafficking of the autism-linked R451C NLGN3 protein, to the cell surface.