Detailing and modeling dendritic spine pruning pathways and cognition in Rab39b XLID mouse model

Human intellectual disability is a common and highly heterogeneous paediatric disorder with a frequency of 2 to 3%, with very severe medical and social problems worldwide. Intellectual disability, as other neurodevelopmental disorders, is mainly characterized by the alterations in neuronal dendritic spine development - shape and/or number - suggesting that abnormalities in dendritic spines are a common hallmark for disorders that include deficits in cognition and information processing. Scientific research conducted on these pathologies is essential to fully dissect the molecular networks controlling spine development, remodelling and maintenance, to define the aetiology of the diseases and then to identify a possible therapy. RAB39B is one of the genes responsible for Intellectual Disability associated with Autism Spectrum Disorders. It encodes for a small GTPases that if absent causes defects in proper spine development, remodeling and maturation, reflected by alterations in cognitive performances in a mouse model. The principal aim of the project focuses to define the specific step of the protein cascade affected by the lack of RAB39B, to delineate the molecular mechanism responsible of neuronal dendritic spine remodeling and maturation. Secondly the project aims to modulate the defined step with specific molecules. In this way, we will cover the major gap on intellectual disability, where the complexity of the cellular processes to treat is the answer for the absence of effective therapies.