The group, led by the Ikerbasque professor Ugo Mayor of the UPV/EHU’s Department of Biochemistry and Molecular Biology, has just published in the journal Human Molecular Genetics an explanation of the mechanisms affected by Angelman syndrome. Thanks to an innovative, experimental design and the state-of-the-art infrastructure of the UPV/EHU’s General Proteomics Research Service, they have managed to identify the changes in the proteins altered by the UBE3A enzyme, the malfunctioning of which in the brain leads to the disease.

According to these new results, UBE3A is responsible for regulating the function of proteasome, a kind of shredding machine that regulates the balance of the other proteins in the cells.  In this indirect way, UBE3A is responsible for the stability of a huge number of processes that take place within the cells. When there is a fault in the UBE3A, these processes do not take place correctly. This explains the complexity of the syndrome that emerges when the UBE3A enzyme fails to perform its function properly. The genetic origin and symptoms of this disease have been studied previously, but until now no explanation has been forthcoming as to how a single gene was capable of creating so many alternations in brain function.

Angelman syndrome is a disease affecting one in every 15,000 newborn babies. It causes complex problems in the intellectual development of children, epilepsy, as well as difficulties in communicating, lack of motor coordination and problems in balance and movement accompanied by extremely few hours of sleep. All this is caused by the failure in the brain of a single gene: UBE3A.

The Angelman Syndrome Association, a key player

Ugo Mayor’s laboratory has been working on this subject since 2012. These studies have been mostly funded by the American foundation, March of Dimes, and MINECO (Spanish Ministry of Economy, Industry and Competitiveness). But despite being to a lesser degree, the funding offered by the association of relatives of people with the disease, the Angelman Syndrome Association, has been a key player in being able to bring this work to a successful conclusion. At a critical moment when Dr Mayor’s laboratory lacked any other backing, this funding was essential in enabling this project to be carried out with the outcomes that have now been published in the prestigious journal Human Molecular Genetics.

Ugo Mayor, an Ikerbasque professor in the UPV/EHU’s Faculty of Science and Technology, wrote up his PhD thesis at Cambridge University, and after 11 years in the United Kingdom, returned to the Basque Country to work at CIC bioGUNE for 5 years. Since 2014 his research group has been part of the Department of Biochemistry and Molecular Biology of the UPV/EHU’s Faculty of Science and Technology.