Article
Chemistry, Medicinal
Bo Huang, Li Zhou, Ruochuan Liu, Lei Wang, Songyi Xue, Yan Shi, Geon Ho Jeong, In Ho Jeong, Sihao Li, Jun Yin, Jianfeng Cai
Summary: This study presents an alternative strategy to PROTACs and molecular glues by constructing and screening a peptide library, leading to the discovery of a peptide P6 that can stimulate the ubiquitin ligase activity of E6AP and accelerate the degradation of its substrate proteins. This approach demonstrates the feasibility of using synthetic ligands to enhance E3 activities in the cell, which can be developed alongside E3 inhibitors and substrate recruiters for drug development.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
R. Mezzena, C. Masciullo, S. Antonini, F. Cremisi, M. Scheffner, M. Cecchini, I Tonazzini
Summary: During neuronal development, focal adhesions play a key role in integrating external signals and promoting neuronal pathfinding and migration. The ubiquitin ligase UBE3A has a crucial function in the nervous system, and changes in its expression levels can lead to neurodevelopmental disorders. Studies using nano/micro-structured anisotropic substrates have shown deficits in contact guidance in cells with UBE3A deficiency.
Article
Neurosciences
Elizabeth L. Berg, Shekib A. Jami, Stela P. Petkova, Annuska Berz, Timothy A. Fenton, Jason P. Lerch, David J. Segal, John A. Gray, Jacob Ellegood, Markus Woehr, Jill L. Silverman
Summary: Angelman syndrome is a rare genetic neurodevelopmental disorder characterized by intellectual disabilities, motor deficits, impaired communication, and happy demeanor; researchers discovered excessive laughter-like ultrasonic emissions in a rat model of AS, suggesting an excitable, playful personality similar to individuals with AS. The unique phenotypes of this rat model, including aberrant social interactions and cognitive impairments, provide advantages for evaluating therapies for AS compared to available mouse models.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Ana Moreira-de-Sa, Francisco Q. Goncalves, Joao P. Lopes, Henrique B. Silva, Angelo R. Tome, Rodrigo A. Cunha, Paula M. Canas
Summary: Research suggests that administration of A(2A) receptor antagonists can improve motor deficits in an Angelman syndrome mouse model and correct synaptic alterations in the cerebellum and striatum.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Genetics & Heredity
Meimiao Fang, Yali Li, Jin Ren, Ronggui Hu, Xiaobo Gao, Liang Chen
Summary: The study revealed a novel role for UBE3A in regulating downstream genes of the retinoic acid signaling pathway, potentially shedding light on a drug target for Angelman syndrome.
FRONTIERS IN GENETICS
(2021)
Article
Behavioral Sciences
Andie Dodge, Jonathan Willman, Matthew Willman, Austin W. Nenninger, Nicole K. Morrill, Kristina Lamens, Hayden Greene, Edwin J. Weeber, Kevin R. Nash
Summary: Angelman syndrome is a rare genetic disorder caused by disruptions to the maternally inherited allele UBE3A. The disorder presents severe and lifelong symptoms, including intractable seizures, abnormal EEG's, ataxic gait, lack of speech, and a notably happy demeanor. Research on the neurophysiological underpinnings of UBE3A in Angelman Syndrome is ongoing to elucidate potential therapeutic targets.
Review
Genetics & Heredity
Jessica Duis, Mark Nespeca, Jane Summers, Lynne Bird, Karen G. C. B. Bindels-de Heus, M. J. Valstar, Marie-Claire Y. de Wit, C. Navis, Maartje ten Hooven-Radstaake, Bianca M. van Iperen-Kolk, Susan Ernst, Melina Dendrinos, Terry Katz, Gloria Diaz-Medina, Akshat Katyayan, Srishti Nangia, Ronald Thibert, Daniel Glaze, Christopher Keary, Karine Pelc, Nicole Simon, Anjali Sadhwani, Helen Heussler, Anne Wheeler, Caroline Woeber, Margaret DeRamus, Amy Thomas, Emily Kertcher, Lauren DeValk, Kristen Kalemeris, Kara Arps, Carol Baym, Nicole Harris, John P. Gorham, Brenda L. Bohnsack, Reid C. Chambers, Sarah Harris, Henry G. Chambers, Katherine Okoniewski, Elizabeth R. Jalazo, Allyson Berent, Carlos A. Bacino, Charles Williams, Anne Anderson
Summary: This article proposes a consensus statement and comprehensive literature review for the management of Angelman syndrome (AS), providing a framework for standardizing care practices. This is crucial at a critical time when new disease-modifying therapies are emerging.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Chao-Wen Lin, Yi-Chun Cheng, Chang-Hao Yang, Hsien-Sung Huang
Summary: This study found that extended exposure to white or blue light can promote the expression of the Angelman syndrome-related gene UBE3A in the retina but not in the visual cortex. Additionally, it was observed that this light exposure caused changes in the chromatin structure of the Ube3a promoter, which further impacted gene expression.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Dilara Sen, Zuzana Drobna, Albert J. Keung
Summary: This study evaluated the specificities of seven commercial UBE3A antibodies and found that three of them showed substantial nonspecific immunoreactivity. While four antibodies demonstrated specific localization patterns in both mouse brain sections and human cerebral organoids, they varied significantly in background signals and staining patterns in undifferentiated human pluripotent stem cells.
SCIENTIFIC REPORTS
(2021)
Article
Cell & Tissue Engineering
Marwa Elamin, Aurelie Dumarchey, Christopher Stoddard, Tiwanna M. Robinson, Christopher Cowie, Dea Gorka, Stormy J. Chamberlain, Eric S. Levine
Summary: Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder characterized by autism and epilepsy. UBE3A, an imprinted gene expressed only from the maternal allele, is believed to be a major driver of Dup15q. In this study, Dup15q neurons showed increased excitability compared to control neurons, and normalizing UBE3A levels using antisense oligonucleotides prevented this phenotype. However, UBE3A overexpression resulted in a similar profile to Dup15q neurons, suggesting the involvement of other genes in the duplicated region.
Article
Neurosciences
James J. Fink, Jeremy D. Schreiner, Judy E. Bloom, Jadin James, Dylan S. Baker, Tiwanna M. Robinson, Richard Lieberman, Leslie M. Loew, Stormy J. Chamberlain, Eric S. Levine
Summary: The study investigated electrophysiological phenotypes in induced pluripotent stem cell-derived neurons from patients with Dup15q, revealing several potential mechanisms of neuronal hyperexcitability and seizure susceptibility. These findings may offer new targets for the treatment of seizures and other associated phenotypes in Dup15q.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Cell Biology
Linn Amanda Syding, Agnieszka Kubik-Zahorodna, Petr Nickl, Vendula Novosadova, Jana Kopkanova, Petr Kasparek, Jan Prochazka, Radislav Sedlacek
Summary: A novel mouse model with a complete deletion of the Ube3a gene exhibits important phenotypes characteristic of Angelman syndrome, including motor dysfunction and behavioral abnormalities.
Article
Genetics & Heredity
Xuechao Zhao, Yuting Zheng, Li Wang, Yanhong Wang, Shiyue Mei, Xiangdong Kong
Summary: A novel UBE3A gene variant was identified in a Chinese family with multigenerational intellectual disability and developmental delay, expanding the genotypic spectrum of Angelman syndrome and providing important information for genetic counseling.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Genetics & Heredity
Xiaonan Du, Ji Wang, Shuang Li, Yu Ma, Tianqi Wang, Bingbing Wu, Yuanfeng Zhou, Lifei Yu, Yi Wang
Summary: This study assessed the phenotype and genotype of Chinese children with Angelman syndrome and found that the majority of patients had maternal deletions and an expanded mutation spectrum for UBE3A variants. Patients in the deletion group had earlier diagnosis, more severe clinical phenotype, and higher rates of epilepsy with multiple seizure types and medication use.
Article
Behavioral Sciences
Peter A. Perrino, Stormy J. Chamberlain, Inge-Marie Eigsti, Roslyn Holly Fitch
Summary: In this study, the researchers investigated the characteristics of Angelman syndrome in a mouse model, focusing on motor deficits, social impairment, rapid auditory processing ability, and altered ultrasonic vocalizations. They found that AS mice exhibited social and motor deficits, as well as marginal enhancements in rapid auditory processing. The study also revealed a correlation between motor impairments and communication impairments in AS, indicating the potential underlying factors contributing to the disorder.
BRAIN AND BEHAVIOR
(2021)
Meeting Abstract
Oncology
J. P. Obeid, R. Stoyanova, M. Patel, K. R. Padgett, J. Slingerland, C. Takita, A. Pollack, N. Alperin, M. Yepes, Y. Zeidan
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2015)
Meeting Abstract
Oncology
R. Stoyanova, S. Abraham, A. Breto, Z. Ao, A. Williams, J. Torres Munoz, R. Datar, R. Cote, Y. Zeidan, A. S. Ishkanian, M. C. Abramowitz, A. Pollack
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2015)
Meeting Abstract
Oncology
S. Gajjar, A. Yoga, I. Reis, Y. Zeidan, C. Takita
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2015)
Article
Oncology
J. -P. Obeid, R. Stoyanova, D. Kwon, M. Patel, K. Padgett, J. Slingerland, C. Takita, N. Alperin, M. Yepes, Y. H. Zeidan
CLINICAL & TRANSLATIONAL ONCOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Anis Ahmad, Alla Mitrofanova, Jacek Bielawski, Yidong Yang, Brian Marples, Alessia Fornoni, Youssef H. Zeidan
Review
Biochemistry & Molecular Biology
Alaa Abou Daher, Tatiana El Jalkh, Assaad A. Eid, Alessia Fornoni, Brian Marples, Youssef H. Zeidan
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2017)
Meeting Abstract
Oncology
A. Ahmad, A. Mitrofanova, A. Fornoni, A. Eid, B. Marples, Y. Zeidan
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2017)
Meeting Abstract
Oncology
J. P. Obeid, R. Stoyanova, Y. Zeidan
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2017)
Review
Oncology
Alissar El Chediak, Ali Shamseddine, Larry Bodgi, Jean-Pierre Obeid, Fady Geara, Youssef H. Zeidan
Article
Oncology
Jean-Pierre Obeid, Radka Stoyanova, Youssef H. Zeidan
TRANSLATIONAL CANCER RESEARCH
(2017)
Review
Oncology
Lara Hilal, Karine A. Al Feghali, Paul Ramia, Ibrahim Abu Gheida, Jean-Pierre Obeid, Wassim Jalbout, Bassem Youssef, Fady Geara, Youssef H. Zeidan
FRONTIERS IN ONCOLOGY
(2017)
Article
Oncology
Youssef H. Zeidan, Joyce G. Habib, Lieveke Ameye, Marianne Paesmans, Evandro de Azambuja, Richard D. Gelber, Ian Campbell, Bo Nordenskjold, Jorge Gutierez, Michael Anderson, Ana Lluch, Michael Gnant, Aron Goldhirsch, Angelo Di Leo, David J. Joseph, John Crown, Martine Piccart-Gebhart, Prudence A. Francis
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2018)
Editorial Material
Oncology
Youssef H. Zeidan, Joyce G. Habib, Evandro de Azambuja, Ian Campbell, Michael Andersson, Ana Lluch, Angelo Di Leo, Prudence A. Francis
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2018)
Meeting Abstract
Oncology
Alla Mitrofanova, Saba Ansari, Thirupandiyur Udayakumar, Jacek Bielawski, Alan Pollack, Alesia Fornoni, Brian Marples, Youssef Zeidan