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Protein shapeshifting in necroptotic cell death signaling.
Trends Biochem Sci
December 2024
Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia. Electronic address:
Necroptosis is a mode of programmed cell death executed by the mixed lineage kinase domain-like (MLKL) pseudokinase following its activation by the upstream receptor-interacting protein kinase-3 (RIPK3), subsequent to activation of death, Toll-like, and pathogen receptors. The pathway originates in innate immunity, although interest has surged in therapeutically targeting necroptosis owing to its dysregulation in inflammatory diseases. Here, we explore how protein conformation and higher order assembly of the pathway effectors - Z-DNA-binding protein-1 (ZBP1), RIPK1, RIPK3, and MLKL - can be modulated by post-translational modifications, such as phosphorylation, ubiquitylation, and lipidation, and intermolecular interactions to tune activities and modulate necroptotic signaling flux.
View Article and Find Full Text PDFNew Strategies to Combat Human Fungal Infections.
J Fungi (Basel)
December 2024
Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, RJ, Brazil.
Over the past few decades, numerous reports have highlighted the significant rise in fungal infections worldwide, contributing to considerable morbidity, mortality, and escalating healthcare costs [...
View Article and Find Full Text PDFPotential of traditional Chinese medicine lyophilized powder of in the treatment of hyperuricemia.
World J Clin Cases
December 2024
Department of Ultrasound imaging, The First Affiliated Hospital of Xiamen University, Xiamen 361000, Fujian Province, China.
Traditional Chinese medicine has a long and illustrious history, and with the development of modern science and technology, the research and application of traditional Chinese medicines have continued to progress significantly. Many traditional Chinese medicinal herbs have undergone scientific validation, reinvigorating with new life and vitality, and contributing unique strengths to the advancement of human health. Recently, the discovery that leech total protein extracted from lyophilized powder reduces blood uric acid (UA) levels by inhibiting the activity of xanthine oxidase to decrease UA synthesis and promotes UA excretion by regulating different UA transporters in the kidney and intestine has undoubtedly injected new vitality and hope into this field of research.
View Article and Find Full Text PDFPulmonary consequences of experimentally induced stroke: differences between global and focal cerebral ischemia.
Front Physiol
December 2024
Department of Medical Physics and Medical Informatics, University of Szeged, Szeged, Hungary.
Introduction: Cerebral ischemia leads to multiple organ dysfunctions, with the lungs among the most severely affected. Although adverse pulmonary consequences contribute significantly to reduced life expectancy after stroke, the impact of global or focal cerebral ischemia on respiratory mechanical parameters remains poorly understood.
Methods: Rats were randomly assigned to undergo surgery to induce permanent global cerebral ischemia (2VO) or focal cerebral ischemia (MCAO), or to receive a sham operation (SHAM).
SUMO2 rescues neuronal and glial cells from the toxicity of P301L Tau mutant.
Front Cell Neurosci
December 2024
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Introduction: Abnormal intracellular accumulation of Tau aggregates is a hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau deposits primarily affect neurons, but evidence indicates that glial cells may also be affected and contribute distinctively to disease progression. Cells can respond to toxic insults by orchestrating global changes in posttranslational modifications of their proteome.
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