Intracellular amyloid toxicity induces oxytosis/ferroptosis regulated cell death.
Ling Huang,Daniel B. McClatchy,Pamela Maher,Zhibin Liang,Jolene K. Diedrich,David Soriano-Castell,Joshua Goldberg,Maxim N. Shokhirev,John R. Yates,David Schubert,Antonio Currais +10 more
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TLDR
It was found that intracellular Aβ induces profound changes in the omics landscape of nerve cells that are associated with a pro-inflammatory, metabolic reprogramming that predisposes cells to die via the oxytosis/ferroptosis regulated cell death pathway in the AD brain.Abstract:
Amyloid beta (Aβ) accumulates within neurons in the brains of early stage Alzheimer’s disease (AD) patients. However, the mechanism underlying its toxicity remains unclear. Here, a triple omics approach was used to integrate transcriptomic, proteomic, and metabolomic data collected from a nerve cell model of the toxic intracellular aggregation of Aβ. It was found that intracellular Aβ induces profound changes in the omics landscape of nerve cells that are associated with a pro-inflammatory, metabolic reprogramming that predisposes cells to die via the oxytosis/ferroptosis regulated cell death pathway. Notably, the degenerative process included substantial alterations in glucose metabolism and mitochondrial bioenergetics. Our findings have implications for the understanding of the basic biology of proteotoxicity, aging, and AD as well as for the development of future therapeutic interventions designed to target the oxytosis/ferroptosis regulated cell death pathway in the AD brain.read more
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Ferroptosis-Related Long Non-Coding RNA signature predicts the prognosis of Head and neck squamous cell carcinoma.
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The critical role and molecular mechanisms of ferroptosis in antioxidant systems: a narrative review
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References
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Journal ArticleDOI
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Scott J. Dixon,Kathryn M. Lemberg,Michael R. Lamprecht,Rachid Skouta,Eleina M. Zaitsev,Caroline E Gleason,Darpan N Patel,Andras J. Bauer,Alexandra M. Cantley,Wan Seok Yang,Barclay Morrison,Brent R. Stockwell,Brent R. Stockwell +12 more
TL;DR: This paper identified the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes.
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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Brent R. Stockwell,José Pedro Friedmann Angeli,Hülya Bayır,Ashley I. Bush,Marcus Conrad,Scott J. Dixon,Simone Fulda,Susan Gascon,Stavroula K. Hatzios,Valerian E. Kagan,Kay Noel,Xuejun Jiang,Andreas Linkermann,Maureen E. Murphy,Michael Overholtzer,Atsushi Oyagi,Gabriela Carolina Pagnussat,Jason Park,Qitao Ran,Craig S. Rosenfeld,Konstantin Salnikow,Daolin Tang,Daolin Tang,Frank M. Torti,Suzy V. Torti,Shinya Toyokuni,K. A. Woerpel,Donna D. Zhang +27 more
TL;DR: The mechanisms underlying ferroptosis are reviewed, connections to other areas of biology and medicine are highlighted, and tools and guidelines for studying this emerging form of regulated cell death are recommended.
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A subcellular map of the human proteome
Peter Thul,Lovisa Åkesson,Mikaela Wiking,Diana Mahdessian,Aikaterini Geladaki,Hammou Ait Blal,Tove Alm,Anna Asplund,Lars Björk,Lisa M. Breckels,Anna Bäckström,Frida Danielsson,Linn Fagerberg,Jenny Fall,Laurent Gatto,Christian Gnann,Sophia Hober,Martin Hjelmare,Fredric Johansson,Sunjae Lee,Cecilia Lindskog,Jan Mulder,Claire M. Mulvey,Peter Nilsson,Per Oksvold,Johan Rockberg,Rutger Schutten,Jochen M. Schwenk,Åsa Sivertsson,Evelina Sjöstedt,Marie Skogs,Charlotte Stadler,Devin P. Sullivan,Hanna Tegel,Casper F. Winsnes,Cheng Zhang,Martin Zwahlen,Adil Mardinoglu,Fredrik Pontén,Kalle von Feilitzen,Kathryn S. Lilley,Mathias Uhlén,Emma Lundberg +42 more
TL;DR: A subcellular map of the human proteome is presented to facilitate functional exploration of individual proteins and their role in human biology and disease and integrated into existing network models of protein-protein interactions for increased accuracy.
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Intracellular amyloid-β in Alzheimer's disease
TL;DR: Although the classical view is that Aβ is deposited extracellularly, emerging evidence from transgenic mice and human patients indicates that this peptide can also accumulate intraneuronally, which may contribute to disease progression.
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DTASelect and Contrast: Tools for Assembling and Comparing Protein Identifications from Shotgun Proteomics
TL;DR: DTASelect, a new software package, assembles SEQUEST identifications and highlights the most significant matches, and the accompanying Contrast tool compares DTASelect results from multiple experiments to improve the speed and precision of proteomic data analysis.