Editorial Material
Genetics & Heredity
Ivona Aksentijevich
Summary: Immune responses require a delicate balance - too weak or too strong a response can cause issues. Spleen tyrosine kinase plays a crucial role in multiple signaling pathways, and its gain-of-function alterations can lead to various problems, including hypogammaglobulinemia and predisposition to B cell lymphoma.
Article
Biochemistry & Molecular Biology
Helen T. Hobbs, Neel H. Shah, Jean M. Badroos, Christine L. Gee, Susan Marqusee, John Kuriyan
Summary: The catalytic activity of Syk-family tyrosine kinases is regulated by a tandem Src homology 2 module, which differs in conformational dynamics from ZAP-70, impacting the stability of its autoinhibited state and potentially influencing downstream signaling pathways in T cells.
Article
Biochemistry & Molecular Biology
Teresa Sadras, Mickael Martin, Kohei Kume, Mark E. Robinson, Supraja Saravanakumar, Gal Lenz, Zhengshan Chen, Joo Y. Song, Tanya Siddiqi, Laura Oksa, Anne Marie Knapp, Jevon Cutler, Kadriye Nehir Cosgun, Lars Klemm, Veronika Ecker, Janet Winchester, Dana Ghergus, Pauline Soulas-Sprauel, Friedemann Kiefer, Nora Heisterkamp, Akhilesh Pandey, Vu Ngo, Lili Wang, Hassan Jumaa, Maike Buchner, Jurgen Ruland, Wing-Chung Chan, Eric Meffre, Thierry Martin, Markus Muschen
Summary: Although SYK and ZAP70 kinases share high sequence homology and serve analogous functions, their expression in B and T cells is strictly segregated throughout evolution. Aberrant ZAP70 expression is identified as a common feature in various B cell malignancies. The strict segregation of the two kinases is crucial for normal B cell selection and acts as a central safeguard against autoimmune diseases and B cell malignancies.
Article
Chemistry, Medicinal
Victor Masip, Angel Lirio, Albert Sanchez-Lopez, Ana B. Cuenca, Raimon Puig de la Bellacasa, Pau Abrisqueta, Jordi Teixido, Jose Borrell, Albert Gibert, Roger Estrada-Tejedor
Summary: Pyrido[2,3-d]pyrimidin-7(8H)-ones have drawn widespread interest as tyrosine kinase inhibitors, with a general synthetic methodology described for the synthesis of 4-substituted-2-(phenylamino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones. The resulting compounds, including N-alkyl, N-aryl, O-aryl, S-aryl, aryl, and aryethynyl substituents at C4, have shown potential biological activity as ZAP-70 inhibitors.
Article
Multidisciplinary Sciences
Jae Sung Ko, Dongjin Jeong, Jaemoon Koh, Hyeryeon Jung, Kyeong Cheon Jung, Yoon Kyung Jeon, Hye Young Kim, Eugene C. Yi, Ho Lee, Chang-Woo Lee, Doo Hyun Chung
Summary: Ssu72 regulates the fine-tuning of TCR signaling by acting as a tyrosine phosphatase for ZAP-70. Ssu72 deficiency leads to hyperresponsiveness in T cells upon TCR stimulation due to increased ZAP-70 phosphorylation, which can be restored by reducing ZAP-70 phosphorylation levels. Additionally, Cd4-CreSsu72fl/fl mice show defects in thymic development and alterations in peripheral T cell populations, with a predisposition for spontaneous inflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Gina Perrella, Samantha J. Montague, Helena C. Brown, Lourdes Garcia Quintanilla, Alexandre Slater, David Stegner, Mark Thomas, Johan W. M. Heemskerk, Steve P. Watson
Summary: The study shows that Syk tyrosine kinase regulates the stability of thrombus under flow conditions, and this process involves pathways additional to activation of GPVI by collagen.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hui Yang, Wei Sun, Yan-nan Fan, Shu-yi Li, Ji-qiao Yuan, Zi-qian Zhang, Xu-yu Li, Ming-bao Lin, Qi Hou
Summary: Perilla leaf extract (PLE) exhibits anti-allergic asthma effects by attenuating airway inflammation and might partly mediate through inhibiting the Syk pathway.
MEDIATORS OF INFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Hannah Ennerfelt, Elizabeth L. Frost, Daniel A. Shapiro, Coco Holliday, Kristine E. Zengeler, Gabrielle Voithofer, Ashley C. Bolte, Catherine R. Lammert, Joshua A. Kulas, Tyler K. Ulland, John R. Lukens
Summary: Recent studies have highlighted the critical roles of microglia and their receptors in controlling neurotoxic material in neurodegenerative diseases. SYK plays an important role in neuroprotective functions of microglia, with its deletion exacerbating AD deposition and neuropathology. In addition, SYK regulates microglial phagocytosis and DAM acquisition in demyelinating disease.
Review
Biochemistry & Molecular Biology
Zhaozhao Wang, Shu Qu, Jiahao Yuan, Wen Tian, Jinglei Xu, Rui Tao, Shilong Sun, Tao Lu, Weifang Tang, Yong Zhu
Summary: This article reviews the biological function of spleen tyrosine kinase (SYK), its relationship with diseases, and therapies targeting SYK. It also proposes the development of new therapeutic approaches for targeting SYK using new technologies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Indira Singaram, Ashutosh Sharma, Shashank Pant, Muyun Lihan, Mi-Jeong Park, Melissa Pergande, Pawanthi Buwaneka, Yusi Hu, Nadim Mahmud, You-Me Kim, Stephanie Cologna, Vladimir Gevorgyan, Irum Khan, Emad Tajkhorshid, Wonhwa Cho
Summary: Membrane lipids control the cellular activity of kinases containing the SH2 domain. In this study, new nonlipidic small molecule inhibitors of the lipid-SH2 domain interaction were developed to block the cellular activity of their host proteins. The research shows that targeting lipid-protein interaction is a powerful approach to developing new small molecule drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Immunology
Eszter Kaposztas, Lili Balogh, Attila Mocsai, Eva Kemecsei, Zoltan Jakus, Tamas Nemeth
Summary: Autoimmune arthritis, such as rheumatoid arthritis, affects a significant portion of the population and current therapies often fail to provide complete relief. Research suggests that inhibiting Syk tyrosine kinase can effectively reduce joint inflammation, mainly by targeting neutrophil functions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Li Li, Xulin Xu, Keyu Lv, Guijuan Zheng, Hao Wang, Shuai Chen, Lang Huang, Yi Liu, Yadong Zhang, Zhaoming Tang, Lili Zhang, Jinyu Wang, Jianlin Qiao, Hongliang Li, Xuanbin Wang, Guangmin Yao, Chao Fang
Summary: Asebogenin exhibits potent antithrombotic effects by inhibiting platelet activation and neutrophil extracellular trap formation, and its mechanism of action is mediated by targeting Syk.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Tony J. Zheng, Elizabeth R. Lofurno, Alexander R. Melrose, Hari Hara Sudhan Lakshmanan, Jiaqing Pang, Kevin G. Phillips, Meghan E. Fallon, Tia C. L. Kohs, Anh T. P. Ngo, Joseph J. Shatzel, Monica T. Hinds, Owen J. T. McCarty, Joseph E. Aslan
Summary: Our study indicates that TKIs targeting Syk or BTK inhibit central platelet functional responses but may differentially affect protein activities and organization in critical systems downstream of Syk and BTK in platelets.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Cell Biology
Xuejiao Chen, Ziyi Wang, Sheng Han, Zeng Wang, Yu Zhang, Xiangdong Li, Nan Xia, Wenjie Yu, Chenyang Jia, Yong Ni, Liyong Pu
Summary: Liver fibrosis is a danger signal for liver cancer, but there is no effective clinical means to regulate its progress. It has been found that inhibiting SYK in monocyte-derived macrophages may help alleviate chronic liver fibrosis.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Daisuke Tsukui, Yoshitaka Kimura, Hajime Kono
Summary: Atherosclerosis complicates chronic inflammatory diseases by involving a shared physiological pathway regulated by spleen tyrosine kinase (SYK). SYK is found to be involved in atherosclerosis via the inflammatory response. Knockout of SYK gene in atherosclerosis-prone mice reduces atherosclerosis in vivo and ameliorates cell migration in macrophages. CD11c expression on SYK-knockout monocytes and macrophages is regulated by forkhead box protein O1 (FOXO1) through granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation, mediated by c-Jun amino-terminal kinase (JNK) signaling to FOXO1. Inhibiting FOXO1 alleviates atherosclerosis in mice, suggesting GM-CSF receptor/SYK/JNK/FOXO1/CD11c signaling and FOXO1 as potential therapeutic targets for atherosclerosis and inflammatory diseases.
Article
Biochemistry & Molecular Biology
Philippe Aubert, Elena Oleynikova, Hina Rizvi, Marieme Ndjim, Catherine Le Berre-Scoul, Pierre Antoine Grohard, Julien Chevalier, Jean-Pierre Segain, Gwenola Le Drean, Michel Neunlist, Helene Boudin
Article
Immunology
Wenjun Liang, Junying Zhang, Margaux Saint-Martin, Fei Xu, Nelly Noraz, Jianmei Liu, Jerome Honnorat, Heli Liu
JOURNAL OF AUTOIMMUNITY
(2019)
Article
Medicine, Research & Experimental
Eric Hatterer, Leticia Barba, Nelly Noraz, Bruno Daubeuf, Jean-Pierre Aubry-Lachainaye, Benoit von der Weid, Francoise Richard, Marie Kosco-Vilbois, Walter Ferlin, Limin Shang, Vanessa Buatois
Article
Immunology
Marion Rincel, Philippe Aubert, Julien Chevalier, Pierre-Antoine Grohard, Lilian Basso, Camille Monchaux de Oliveira, Jean Christophe Helbling, Elodie Levy, Gregoire Chevalier, Marion Leboyer, Gerard Eberl, Sophie Laye, Lucile Capuron, Nathalie Vergnolle, Michel Neunlist, Helene Boudin, Patricia Lepage, Muriel Darnaudery
BRAIN BEHAVIOR AND IMMUNITY
(2019)
Article
Immunology
Margaux Saint-Martin, Alanah Pieters, Benoit Dechelotte, Celine Malleval, Delphine Pinatel, Olivier Pascual, Domna Karagogeos, Jerome Honnorat, Veronique Pellier-Monnin, Nelly Noraz
JOURNAL OF AUTOIMMUNITY
(2019)
Review
Biochemistry & Molecular Biology
Hiroshi Mitoma, Jerome Honnorat, Kazuhiko Yamaguchi, Mario Manto
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Multidisciplinary Sciences
Jacques Gonzales, Catherine Le Berre-Scoul, Anne Dariel, Paul Breheret, Michel Neunlist, Helene Boudin
SCIENTIFIC REPORTS
(2020)
Article
Microbiology
Jacques Gonzales, Justine Marchix, Laetitia Aymeric, Catherine Le Berre-Scoul, Johanna Zoppi, Philippe Bordron, Marie Burel, Laetitia Davidovic, Jean-Romain Richard, Alexandru Gaman, Florian Lejuste, Julie Z. Brouillet, Francoise Le Vacon, Samuel Chaffron, Marion Leboyer, Helene Boudin, Michel Neunlist
Summary: Research indicated that changes in the microbiota composition in adult ASD patients may lead to gastrointestinal alterations and remodeling of the enteric nervous system (ENS).
Review
Biochemistry & Molecular Biology
Nicolas Lundahl Ciano-Petersen, Pablo Cabezudo-Garcia, Sergio Muniz-Castrillo, Jerome Honnorat, Pedro Jesus Serrano-Castro, Begona Oliver-Martos
Summary: Discovery of biomarkers in rare diseases, like anti-NMDAR encephalitis, is crucial for better diagnosis, prognosis, and treatment development. Clinical and paraclinical markers are widely explored, while soluble molecules are proposed as biomarkers for clinical activity, inflammation, prognosis, and treatment response, requiring further studies for clinical validation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Hiroshi Mitoma, Kazuhiko Yamaguchi, Jerome Honnorat, Mario Manto
Summary: Long-term depression at parallel fibers-Purkinje cells (PF-PC LTD) is crucial for cerebellar motor learning and control. Dysregulation of PF-PC LTD has been identified as a factor in immune-mediated cerebellar ataxias and spinocerebellar ataxias, leading to impaired adaptive behaviors. LTDpathy is a clinical concept that encompasses these conditions characterized by PF-PC LTD dysfunction and related adaptive behavior impairments.
Article
Clinical Neurology
Elise Peter, Le Duy Do, Salem Hannoun, Sergio Muniz-Castrillo, Alberto Vogrig, Valentin Wucher, Anne-Laurie Pinto, Naura Chounlamountri, Walaa Zakaria, Veronique Rogemond, Geraldine Picard, Julien-Jacques Hedou, Aditya Ambati, Agusti Alentorn, Alexandra Traverse-Glehen, Mario Manto, Dimitri Psimaras, Emmanuel Mignot, Francois Cotton, Virginie Desestret, Jerome Honnorat, Bastien Joubert
Summary: This study describes the clinical-immunologic features and long-term outcomes of patients with anti-DNER antibodies. Most patients had cerebellar ataxia and became moderately to severely disabled. Half of the patients improved, and younger age, milder clinical presentations, and less decrease of cerebellar gray matter volumes were associated with a better outcome.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2022)
Review
Biochemistry & Molecular Biology
Tam T. Quach, Harrison J. Stratton, Rajesh Khanna, Sabrina Mackey-Alfonso, Nicolas Deems, Jerome Honnorat, Kathrin Meyer, Anne-Marie Duchemin
Summary: This article provides an overview of neurodegenerative diseases and explores new therapeutic approaches. The accumulation of misfolded/aggregated proteins in the brain is a common pathological feature. The authors suggest a multiplexed gene transfer strategy to extend brain health span and improve chronic disease states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Agusti Alentorn, Giulia Berzero, Harry Alexopoulos, John Tzartos, German Reyes Botero, Andrea Morales Martinez, Sergio Muniz-Castrillo, Alberto Vogrig, Bastien Joubert, Francisco Garcia A. Jimenez, Dagoberto Cabrera, Jose Vladimir Tobon, Carolina Delgado, Patricio Sandoval, Monica Troncoso, Lorna Galleguillos, Marine Giry, Marion Benazra, Isaias Hernandez Verdin, Maelle Dade, Geraldine Picard, Veronique Rogemond, Nicolas Weiss, Marinos C. Dalakas, Pierre-Yves Boelle, Jean-Yves Delattre, Jerome Honnorat, Dimitri Psimaras
Summary: Anti-NMDAR encephalitis is associated with multiple antigenic triggers and this study aimed to explore if geographic and climatic factors may influence disease risk. Through a systematic review and meta-analysis, they found that the incidence of anti-NMDAR encephalitis varies among countries, with higher rates in Oceania and South America compared to Europe and North America. Regression models confirmed a strong negative correlation with latitude and seasonal analyses showed a peak of cases during warm months. Exposure-lag-response models revealed a positive correlation between extreme hot temperatures and disease incidence in France.
Article
Gastroenterology & Hepatology
Emilie Duchalais, Christophe Guilluy, Steven Nedellec, Melissa Touvron, Anne Bessard, Yann Touchefeu, Celine Bossard, Helene Boudin, Guy Louarn, Michel Neunlist, Laurianne Van Landeghem
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2018)