Angelman syndrome: a journey through the brain

• Published in: The FEBS journal Vol. 287; no. 11; pp. 2154 - 2175
• Main Authors: Maranga, Carina, Fernandes, Tiago G., Bekman, Evguenia, da Rocha, Simão Teixeira
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2020
• Subjects: Angelman syndrome; Angelman Syndrome - diagnostic imaging; Angelman Syndrome - genetics; Angelman Syndrome - pathology; Angelman Syndrome - therapy; Animal models; Animals; Ataxia; Brain; Brain - diagnostic imaging; Brain - drug effects; Brain - pathology; Cerebellar Cortex - diagnostic imaging; Cerebellar Cortex - metabolism; Cerebellar Cortex - pathology; Cerebellum; Cerebellum - diagnostic imaging; Cerebellum - metabolism; Cerebellum - pathology; cortex; genes; hippocampus; Hippocampus - diagnostic imaging; Hippocampus - metabolism; Hippocampus - pathology; Humans; Loss of Function Mutation - genetics; Mice; Neurodevelopmental disorders; Neurodevelopmental Disorders - genetics; Neurodevelopmental Disorders - pathology; Neurodevelopmental Disorders - therapy; pathophysiology; Phenotypes; Signs and symptoms; speech; Stem cell transplantation; Stem cells; UBE3A; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - genetics; cortex; Angelman syndrome; UBE3A; hippocampus; cerebellum
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.15258

Angelman syndrome (AS) is an incurable neurodevelopmental disease caused by loss of function of the maternally inherited UBE3A gene. AS is characterized by a defined set of symptoms, namely severe developmental delay, speech impairment, uncontrolled laughter, and ataxia. Current understanding of the pathophysiology of AS relies mostly on studies using the murine model of the disease, although alternative models based on patient‐derived stem cells are now emerging. Here, we summarize the literature of the last decade concerning the three major brain areas that have been the subject of study in the context of AS: hippocampus, cortex, and the cerebellum. Our comprehensive analysis highlights the major phenotypes ascribed to the different brain areas. Moreover, we also discuss the major drawbacks of current models and point out future directions for research in the context of AS, which will hopefully lead us to an effective treatment of this condition in humans. Angelman syndrome is a rare neurodevelopmental disorder that is caused by loss of the maternal UBE3A gene in neurons. In this review, we summarize the last decade of research in the three major brain areas: hippocampus, cortex, and cerebellum. We highlight the major findings for each brain area and the therapeutic targets, and discuss the future directions of research in the context of this disease.