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

Area tematica

Scienze biomediche

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di neuroscienze (IN)

Responsabile di progetto

MATTEO FOSSATI
Telefono: 0282245254
E-mail: 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

Data inizio attività

01/11/2021

Parole chiave

Angelmann, Ube3A, sinapsi

Ultimo aggiornamento: 20/05/2024