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排序方式: 共有595条查询结果,搜索用时 15 毫秒
591.
Mie A. Nordmaj Morgan E. Roberts Emilie S. Sachse Robert Dagil Anne Poder Andersen Nanna Skeltved Kaare V. Grunddal Sayit Mahmut Erdoan Swati Choudhary Tobias Gustsavsson Maj Sofie
rum-Madsen Igor Moskalev Weihua Tian Zhang Yang Thomas M. Clausen Thor G. Theander Mads Daugaard Morten A. Nielsen Ali Salanti 《Cell death & disease》2021,12(4)
As an immune evasion and survival strategy, the Plasmodium falciparum malaria parasite has evolved a protein named VAR2CSA. This protein mediates sequestration of infected red blood cells in the placenta through the interaction with a unique carbohydrate abundantly and exclusively present in the placenta. Cancer cells were found to share the same expression of this distinct carbohydrate, termed oncofetal chondroitin sulfate on their surface. In this study we have used a protein conjugation system to produce a bispecific immune engager, V-aCD3, based on recombinant VAR2CSA as the cancer targeting moiety and an anti-CD3 single-chain variable fragment linked to a single-chain Fc as the immune engager. Conjugation of these two proteins resulted in a single functional moiety that induced immune mediated killing of a broad range of cancer cells in vitro and facilitated tumor arrest in an orthotopic bladder cancer xenograft model.Subject terms: Drug development, Preclinical research 相似文献
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Anne Filipe Alexander Chernorudskiy Sandrine Arbogast Ersilia Varone Rocío-Nur Villar-Quiles Diego Pozzer Maryline Moulin Stefano Fumagalli Eva Cabet Swati Dudhal Maria-Grazia De Simoni Raphaël Denis Nathalie Vadrot Corinne Dill Matteo Giovarelli Luke Szweda Clara De Palma Paolo Pinton Carlotta Giorgi Carlo Viscomi Emilio Clementi Sonia Missiroli Simona Boncompagni Ester Zito Ana Ferreiro 《Cell death and differentiation》2021,28(1):123
SEPN1-related myopathy (SEPN1-RM) is a muscle disorder due to mutations of the SEPN1 gene, which is characterized by muscle weakness and fatigue leading to scoliosis and life-threatening respiratory failure. Core lesions, focal areas of mitochondria depletion in skeletal muscle fibers, are the most common histopathological lesion. SEPN1-RM underlying mechanisms and the precise role of SEPN1 in muscle remained incompletely understood, hindering the development of biomarkers and therapies for this untreatable disease. To investigate the pathophysiological pathways in SEPN1-RM, we performed metabolic studies, calcium and ATP measurements, super-resolution and electron microscopy on in vivo and in vitro models of SEPN1 deficiency as well as muscle biopsies from SEPN1-RM patients. Mouse models of SEPN1 deficiency showed marked alterations in mitochondrial physiology and energy metabolism, suggesting that SEPN1 controls mitochondrial bioenergetics. Moreover, we found that SEPN1 was enriched at the mitochondria-associated membranes (MAM), and was needed for calcium transients between ER and mitochondria, as well as for the integrity of ER-mitochondria contacts. Consistently, loss of SEPN1 in patients was associated with alterations in body composition which correlated with the severity of muscle weakness, and with impaired ER-mitochondria contacts and low ATP levels. Our results indicate a role of SEPN1 as a novel MAM protein involved in mitochondrial bioenergetics. They also identify a systemic bioenergetic component in SEPN1-RM and establish mitochondria as a novel therapeutic target. This role of SEPN1 contributes to explain the fatigue and core lesions in skeletal muscle as well as the body composition abnormalities identified as part of the SEPN1-RM phenotype. Finally, these results point out to an unrecognized interplay between mitochondrial bioenergetics and ER homeostasis in skeletal muscle. They could therefore pave the way to the identification of biomarkers and therapeutic drugs for SEPN1-RM and for other disorders in which muscle ER-mitochondria cross-talk are impaired.Subject terms: Chaperones, Respiratory tract diseases 相似文献
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