The Translational Regulation in mTOR Pathway

Biomolecules, Journal Year: 2022, Volume and Issue: 12(6), P. 802 - 802

Published: June 8, 2022

The mechanistic/mammalian target of rapamycin (mTOR) plays a master role in cell proliferation and growth response to insulin, amino acids, energy levels, oxygen. mTOR can coordinate upstream signals with downstream effectors, including transcriptional translational apparatuses regulate fundamental cellular processes such as utilization, protein synthesis, autophagy, growth, proliferation. Of the above, synthesis is highly energy-consuming; thus, mRNA translation under tight immediate control signaling. regulation driven by signaling mainly relies on eukaryotic initiation factor 4E (eIF4E)-binding (4E-BP), ribosomal S6 kinase (S6K), its players, which are significant rapid environmental change. not only controls general translation, but preferential well. This means that shows stronger selectivity particular mRNAs. Some evidence has supported contribution 4E-BP La-related proteins 1 (LARP1) regulation. In this review, we summarize pathway focus mTOR-mediated We introduce major components their functions or manner, describe how specificity coordinated. Furthermore, recent research progress propose additional ideas for reference. Because center metabolism, comprehensively understanding will contribute therapy related diseases, cancers, type 2 diabetes, obesity, neurodegeneration.

Language: Английский

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Inhibition of S6K lowers age-related inflammation and increases lifespan through the endolysosomal system

Nature Aging, Journal Year: 2024, Volume and Issue: 4(4), P. 491 - 509

Published: Feb. 27, 2024

Suppression of target rapamycin complex 1 (TORC1) by ameliorates aging in diverse species. S6 kinase (S6K) is an essential mediator, but the mechanisms involved are unclear. Here we show that activation S6K specifically Drosophila fat-body blocked extension lifespan rapamycin, induced accumulation multilamellar lysosomes and age-associated hyperactivation NF-κB-like immune deficiency (IMD) pathway, indicative reduced inflammaging. Syntaxin 13 mediated effects TORC1-S6K signaling on lysosome morphology inflammaging, suggesting they may be linked. Inflammaging depended IMD receptor regulatory isoform PGRP-LC, repression pathway from midlife extended lifespan. Age-related inflammaging was higher females than males not lowered treatment or S6K. Rapamycin also elevated 12/13 levels mouse liver prevented age-related increase noncanonical NF-κB signaling, effect TORC1 conserved flies to mammals.

Language: Английский

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Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 97, P. 101270 - 101270

Published: April 6, 2024

The onset of sarcopenia is intimately linked with aging, posing significant implications not only for individual patient quality life but also the broader societal healthcare framework. Early and accurate identification a comprehensive understanding its mechanistic underpinnings therapeutic targets paramount to addressing this condition effectively. This review endeavors present cohesive overview recent advancements in research diagnosis. We initially delve into contemporary diagnostic criteria, specifically referencing European Working Group on Sarcopenia Older People (EWGSOP) 2 Asian (AWGS) 2019 benchmarks. Additionally, we elucidate assessment techniques muscle strength, quantity, physical performance, highlighting tools such as grip chair stand test, dual-energy X-ray Absorptiometry (DEXA), bioelectrical impedance analysis (BIA), gait speed, short performance battery (SPPB), while discussing their inherent advantages limitations. Such pave way early unequivocal diagnosis sarcopenia. Proceeding further, provide deep-dive sarcopenia's pathogenesis, offering thorough examination associated signaling pathways like Myostatin, AMP-activated protein kinase (AMPK), insulin/IGF-1 Signaling (IIS), nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) pathways. Each pathway's role mediation detailed, underscoring potential target avenues. From perspective, underscores pivotal mitochondrial dysfunction sarcopenia, emphasizing elements oxidative overload, biogenesis, mitophagy, significance. At last, capture strides made treatment, ranging from nutritional exercise interventions pharmacological supplementation strategies. In sum, meticulously synthesizes latest scientific developments aiming enhance precision clinical practice insights refined innovative interventions, ultimately contributing optimized care field.

Language: Английский

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Akt and mTOR in B Cell Activation and Differentiation

Frontiers in Immunology, Journal Year: 2012, Volume and Issue: 3

Published: Jan. 1, 2012

Activation of phosphoinositide 3-kinase (PI3K) is required for B cell proliferation and survival. PI3K signaling also controls key aspects differentiation. Upon engagement the receptor (BCR), activation promotes Ca2+ mobilization NFκB-dependent transcription, events which are essential proliferation. initiates a distinct pathway involving Akt mTOR serine/threonine kinases. It has been generally assumed that downstream function. However, have complex roles in fate decisions suppression this can enhance certain responses while repressing others. In review we will discuss genetic pharmacological studies function normal cells, malignancies origin.

Language: Английский

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Dysregulation of Mammalian Target of Rapamycin Signaling in Mouse Models of Autism

Journal of Neuroscience, Journal Year: 2015, Volume and Issue: 35(41), P. 13836 - 13842

Published: Oct. 14, 2015

The mammalian target of rapamycin (mTOR) is a central regulator diverse array cellular processes, including cell growth, proliferation, autophagy, translation, and actin polymerization. Components the mTOR cascade are present at synapses influence synaptic plasticity spine morphogenesis. A prevailing view that study its role in autism spectrum disorders (ASDs) will elucidate molecular mechanisms by which regulates neuronal function under physiological pathological conditions. Although many ASDs arise as result mutations genes with multiple functions, they appear to converge on common biological pathways give rise autism-relevant behaviors. Dysregulation signaling has been identified phenotypic feature fragile X syndrome, tuberous sclerosis complex 1 2, neurofibromatosis 1, phosphatase tensin homolog, potentially Rett syndrome. Below summary topics covered symposium presents dysregulation unifying theme subset ASDs.

Language: Английский

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