Differential functional consequences of GRIN2A mutations associated with schizophrenia and neurodevelopmental disorders

Autor: Nate Shepard, David Baez-Nieto, Sumaiya Iqbal, Erkin Kurganov, Nikita Budnik, Arthur J. Campbell, Jen Q. Pan, Morgan Sheng, Zohreh Farsi

Publikováno v: Scientific Reports, Vol 14, Iss 1, Pp 1-10 (2024)

Abstract Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A, encoding for the GluN2A subunit of the NMDA receptors, that confer significant risk for schizophrenia (SCZ). Mutations in GRIN2A are also associated

Externí odkaz: https://doaj.org/article/ea721aca363248aba72053e8a5a63a85

Characterization of intrinsically disordered regions in proteins informed by human genetic diversity.

Autor: Shehab S Ahmed, Zaara T Rifat, Ruchi Lohia, Arthur J Campbell, A Keith Dunker, M Sohel Rahman, Sumaiya Iqbal

Publikováno v: PLoS Computational Biology, Vol 18, Iss 3, p e1009911 (2022)

All proteomes contain both proteins and polypeptide segments that don't form a defined three-dimensional structure yet are biologically active-called intrinsically disordered proteins and regions (IDPs and IDRs). Most of these IDPs/IDRs lack useful f

Externí odkaz: https://doaj.org/article/f7de1e5e0be544dc8b92e8966a2b313f

Delineation of functionally essential protein regions for 242 neurodevelopmental genes

Autor: Sumaiya Iqbal, Tobias Brünger, Eduardo Pérez-Palma, Marie Macnee, Andreas Brunklaus, Mark J Daly, Arthur J Campbell, David Hoksza, Patrick May, Dennis Lal

Publikováno v: Brain. 146:519-533

Neurodevelopmental disorders (NDDs), including severe paediatric epilepsy, autism and intellectual disabilities are heterogeneous conditions in which clinical genetic testing can often identify a pathogenic variant. For many of them, genetic therapie

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8de97e10b6264507d48ee25dd5c51f65
https://doi.org/10.1093/brain/awac381

Discovery of a First-in-Class Inhibitor of the PRMT5–Substrate Adaptor Interaction

Autor: Dale Porter, Alessandra Ianari, Merissa Brousseau, Patrick McCarren, Foxy P. Robinson, Adam Skepner, Virendar K. Kaushik, Kathleen M. Mulvaney, Arthur J. Campbell, Martin J Drysdale, Zachary Mullin-Bernstein, Brian J. McMillan, Robert Hilgraf, Ritu Singh, Matthew J. Ranaghan, Meghan O’Keefe, William R. Sellers, David C. McKinney, Jamie A. Moroco, Michael F. Mesleh, David E. Timm, Besnik Bajrami, Florence F. Wagner

Publikováno v: J Med Chem

PRMT5 and its substrate adaptor proteins (SAPs), pICln and Riok1, are synthetic lethal dependencies in MTAP-deleted cancer cells. SAPs share a conserved PRMT5 binding motif (PBM) which mediates binding to a surface of PRMT5 distal to the catalytic si

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e2c09646bd9e9db576eb95fa59b4da5
https://doi.org/10.1021/acs.jmedchem.1c00507

Differential excitatory vs inhibitory SCN expression at single cell level regulates brain sodium channel function in neurodevelopmental disorders

Autor: Yinqing Li, Zhanyan Fu, Holger Lerche, Stephen Sanders, Andreas Brunklaus, Xian Adiconis, Joshua Z. Levin, Dennis Lal, Steven A. McCarroll, Miriam H. Meisler, Boaz Barak, Cynthia C. Hession, Reut Shema, Rikke S. Møller, Sean Simmons, Guoping Feng, Juanjiangmeng Du, Arthur J. Campbell

Publikováno v: Du, J, Simmons, S, Brunklaus, A, Adiconis, X, Hession, C C, Fu, Z, Li, Y, Shema, R, Møller, R S, Barak, B, Feng, G, Meisler, M, Sanders, S, Lerche, H, Campbell, A J, McCarroll, S, Levin, J Z & Lal, D 2020, ' Differential excitatory vs inhibitory SCN expression at single cell level regulates brain sodium channel function in neurodevelopmental disorders ', European Journal of Paediatric Neurology, vol. 24, pp. 129-133 . https://doi.org/10.1016/j.ejpn.2019.12.019

The four voltage-gated sodium channels SCN1/2/3/8A have been associated with heterogeneous types of developmental disorders, each presenting with disease specific temporal and cell type specific gene expression. Using single-cell RNA sequencing trans

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da1ce5f7bf63dbbf3614811396306c09
https://doi.org/10.1016/j.ejpn.2019.12.019