Telethon FOSSATI GGP20127 - Investigating The Ube3a-Dependent Sumoylation Imbalance In The Pathogenesis Of The Angelman Syndrome (DSB.AD004.338)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of neuroscience (IN)

Project manager

MATTEO FOSSATI
Phone number: 0282245254
Email: matteo.fossati@in.cnr.it

Abstract

The intellectual disability (ID) is a generalized neurodevelopmental disorder that affects millions of individuals worldwide and represents a major socio-economic burden. Given the complex multifactorial origin of ID, the molecular mechanisms underlying its pathogenesis are largely unknown and, at present, no effective therapies are available. This pilot project will focus on the Angelman syndrome (AS), a genetic form of syndromic ID, characterized by severe intellectual deficit, motor dysfunction, unusually happy demeanor, seizures and autism-like behavior. AS is caused by the loss of UBE3A gene, which encodes the E3 ubiquitin ligase UBE3A. In the brain, ubiquitination regulates multiple synaptic pathways and is critical to generate fully functional neuronal circuits. Emerging evidence indicates that ubiquitination functionally interplays with sumoylation, a ubiquitin-related post-translational modification. Intriguingly, major synaptic targets of UBE3A are also SUMO substrates. In this research program we will explore the hypothesis that defective ubiquitination caused by the loss of UBE3A affects neuronal sumoylation homeostasis, contributing to synaptic dysfunction in AS. Using

Start date of activity

01/11/2021

Keywords

Angelmann, Ube3A, sinapsi

Last update: 19/04/2025