Results 81 to 90 of about 63,525 (265)

A Wacky Bridge to mTORC1 Dimerization [PDF]

open access: yesDevelopmental Cell, 2016
The activity of the mTORC1 protein complex depends on multiple metabolic inputs that regulate dimerization, recruitment to the lysosome, and activation. In this issue of Developmental Cell, David-Morrison et al. (2016) show that the Drosophila protein Wacky and its mammalian counterpart WAC act as adaptors in the process of mTORC1 dimerization.
openaire   +3 more sources

HMGCR‐Driven Cholesterol Metabolism Promotes Osteoarthritis Progression by Accelerating Synovial Fibroblast Senescence

open access: yesAdvanced Science, EarlyView.
In the pathological context of osteoarthritis (OA), the phosphorylation of AKT1 at Ser473 enhances its binding to Lys140 of Insig1, which facilitates the formation of AKT1–Insig1 complex. Subsequently, the activation of AKT1 promotes the phosphorylation of Insig1 at Ser189, potentially enhancing the dissociation of Insig1 from sterol regulatory element‑
Xiaoqi Zhang   +19 more
wiley   +1 more source

Treatment of Primary Aldosteronism with mTORC1 Inhibitors [PDF]

open access: yesYearbook of Paediatric Endocrinology, 2019
Abstract Context Mammalian target of rapamycin complex 1 (mTORC1) activity is often increased in the adrenal cortex of patients with primary aldosteronism (PA), and mTORC1 inhibition decreases aldosterone production in adrenocortical cells, suggesting the mTORC1 pathway as a target for treatment of PA.
Beckey Trinh   +13 more
openaire   +5 more sources

TPI1 Loss Triggers a Metabolite‐Driven Mitochondrial Redox Vulnerability via the SARM1–cADPR–Ca2+ Axis

open access: yesAdvanced Science, EarlyView.
Metabolite‐driven redox stress governs cancer cell senescence. TPI1 deficiency elevates DHAP, initiating SARM1‐dependent cADPR‐Ca2+ release. Mitochondrial ROS surge subsequently induces DNA damage and senescence, offering a conserved therapeutic target in multiple cancers.
Chunyu Liu   +15 more
wiley   +1 more source

Beyond Simple Mimicry: Next‐Generation Geometric Architectures and Future Paradigms in Small‐Molecule and Macrocyclic Peptidomimetics

open access: yesAngewandte Chemie, EarlyView.
Peptide‐to‐Small Molecule Paradigm: Peptidomimetics have evolved from simple mimicry toward drug‐like scaffolds supported by increasing clinical successes. This Perspective highlights the geometric design principles—linear repetition, convergent fusion, and cyclization—defining the next‐generation peptidomimetic architectures capable of targeting ...
Jesang Lee   +5 more
wiley   +2 more sources

Relationship of mTORC1 and ferroptosis in tumors

open access: yesDiscover Oncology
AbstractFerroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors.
Huilin Liao   +9 more
openaire   +3 more sources

Gαi1/3 Are Essential for BMP2‐Induced Osteogenesis by Bridging BMP Receptors to the Gab1 Signaling Complex

open access: yesAdvanced Science, EarlyView.
The Gαi1/3 protein is a crucial connecting protein closely related to the signal transduction process of bone formation‐related cytokines such as BMP2. Gαi1/3 mediates downstream signaling pathways such as Smads and MAPK by binding to adaptor proteins like Gab1, thereby promoting the osteogenic effect of BMSCs.
Huajian Shan   +10 more
wiley   +1 more source

Innovative Test Strip‐Based Colorimetric Sensors Integrated With Affinity Chromatography: Acetylcholinesterase Inhibitor Screening Breakthrough in Lycium Barbarum Leaves

open access: yesAdvanced Science, EarlyView.
Schematic diagrams illustrating the breakthrough in the screening of AChE inhibitors from LBL, and the research process of the pharmacodynamics of the NCP are presented. ABSTRACT Current Alzheimer's drugs exhibit limited effectiveness, highlighting the necessity for multi‐target treatments.
Yuping Sa   +11 more
wiley   +1 more source

Gut‐Liver Translocation of Bacteroides Uniformis Alleviates Advanced Metabolic Dysfunction‐Associated Steatotic Liver Disease by Suppressing Hepatocyte Ferroptosis via Propionic Acid Secretion

open access: yesAdvanced Science, EarlyView.
Systematic characterization of the liver‐resident microbiota in advanced metabolic dysfunction‐associated steatotic liver disease (MASLD) reveals a consistent depletion of Bacteroides uniformis (B. uniformis) in both hepatic and gut microbial communities. Oral gavage of B.
Haiyang Liu   +4 more
wiley   +1 more source

Inhibition of phosphodiesterase 4D suppresses mTORC1 signaling and pancreatic cancer growth

open access: yesJCI Insight, 2023
The mammalian target of rapamycin complex 1 (mTORC1) senses multiple upstream stimuli to orchestrate anabolic and catabolic events that regulate cell growth and metabolism. Hyperactivation of mTORC1 signaling is observed in multiple human diseases; thus,
Mi-Hyeon Jeong   +4 more
doaj   +1 more source

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