Targeted dephosphorylation of SMAD3 as an approach to impede TGF-β signaling

Autor: Abigail Brewer, Jin-Feng Zhao, Rotimi Fasimoye, Natalia Shpiro, Thomas J. Macartney, Nicola T. Wood, Melanie Wightman, Dario R. Alessi, Gopal P. Sapkota

Publikováno v: iScience, Vol 27, Iss 8, Pp 110423- (2024)

Summary: TGF-β (transforming growth factor-β) signaling is involved in a myriad of cellular processes and its dysregulation has been implicated in many human diseases, including fibrosis and cancer. TGF-β transcriptional responses are controlled b

Externí odkaz: https://doaj.org/article/29d5d7de42d54273bca16ac8b4f72fb9

Protein aggregation and calcium dysregulation are hallmarks of familial Parkinson’s disease in midbrain dopaminergic neurons

Autor: Gurvir S. Virdi, Minee L. Choi, James R. Evans, Zhi Yao, Dilan Athauda, Stephanie Strohbuecker, Raja S. Nirujogi, Anna I. Wernick, Noelia Pelegrina-Hidalgo, Craig Leighton, Rebecca S. Saleeb, Olga Kopach, Haya Alrashidi, Daniela Melandri, Jimena Perez-Lloret, Plamena R. Angelova, Sergiy Sylantyev, Simon Eaton, Simon Heales, Dmitri A. Rusakov, Dario R. Alessi, Tilo Kunath, Mathew H. Horrocks, Andrey Y. Abramov, Rickie Patani, Sonia Gandhi

Publikováno v: npj Parkinson's Disease, Vol 8, Iss 1, Pp 1-22 (2022)

Abstract Mutations in the SNCA gene cause autosomal dominant Parkinson’s disease (PD), with loss of dopaminergic neurons in the substantia nigra, and aggregation of α-synuclein. The sequence of molecular events that proceed from an SNCA mutation d

Externí odkaz: https://doaj.org/article/fc1ba7fa6d614cbe962ce2b5a05c4fa6

Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain

Autor: Shahzad S Khan, Yuriko Sobu, Herschel S Dhekne, Francesca Tonelli, Kerryn Berndsen, Dario R Alessi, Suzanne R Pfeffer

Publikováno v: eLife, Vol 10 (2021)

Activating LRRK2 mutations cause Parkinson’s disease, and pathogenic LRRK2 kinase interferes with ciliogenesis. Previously, we showed that cholinergic interneurons of the dorsal striatum lose their cilia in R1441C LRRK2 mutant mice (Dhekne et al.,

Externí odkaz: https://doaj.org/article/c486db2909d74097bd5b26027a1a91b2

A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research.

Autor: Suzannah J Rihn, Andres Merits, Siddharth Bakshi, Matthew L Turnbull, Arthur Wickenhagen, Akira J T Alexander, Carla Baillie, Benjamin Brennan, Fiona Brown, Kirstyn Brunker, Steven R Bryden, Kerry A Burness, Stephen Carmichael, Sarah J Cole, Vanessa M Cowton, Paul Davies, Chris Davis, Giuditta De Lorenzo, Claire L Donald, Mark Dorward, James I Dunlop, Matthew Elliott, Mazigh Fares, Ana da Silva Filipe, Joseph R Freitas, Wilhelm Furnon, Rommel J Gestuveo, Anna Geyer, Daniel Giesel, Daniel M Goldfarb, Nicola Goodman, Rory Gunson, C James Hastie, Vanessa Herder, Joseph Hughes, Clare Johnson, Natasha Johnson, Alain Kohl, Karen Kerr, Hannah Leech, Laura Sandra Lello, Kathy Li, Gauthier Lieber, Xiang Liu, Rajendra Lingala, Colin Loney, Daniel Mair, Marion J McElwee, Steven McFarlane, Jenna Nichols, Kyriaki Nomikou, Anne Orr, Richard J Orton, Massimo Palmarini, Yasmin A Parr, Rute Maria Pinto, Samantha Raggett, Elaine Reid, David L Robertson, Jamie Royle, Natalia Cameron-Ruiz, James G Shepherd, Katherine Smollett, Douglas G Stewart, Meredith Stewart, Elena Sugrue, Agnieszka M Szemiel, Aislynn Taggart, Emma C Thomson, Lily Tong, Leah S Torrie, Rachel Toth, Margus Varjak, Sainan Wang, Stuart G Wilkinson, Paul G Wyatt, Eva Zusinaite, Dario R Alessi, Arvind H Patel, Ali Zaid, Sam J Wilson, Suresh Mahalingam

Publikováno v: PLoS Biology, Vol 19, Iss 2, p e3001091 (2021)

The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In

Externí odkaz: https://doaj.org/article/cc007f107e3a422ab1bfef32714d1945

Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

Autor: Chiara Maniaci, Scott J. Hughes, Andrea Testa, Wenzhang Chen, Douglas J. Lamont, Sonia Rocha, Dario R. Alessi, Roberto Romeo, Alessio Ciulli

Publikováno v: Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017)

Targeting the ubiquitin proteasome system to modulate protein homeostasis using small molecules has promising therapeutic potential. Here the authors describe Homo-PROTACS: small molecules that can induce the homo-dimerization of E3 ubiquitin ligases

Externí odkaz: https://doaj.org/article/ce1eb8bbc3b24cf8a56b68d61eacff1e