Dysregulation of Mammalian Target of Rapamycin Signaling in Mouse Models of Autism DOI Creative Commons
Kimberly M. Huber, Eric Klann, Mauro Costa‐Mattioli

et al.

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

Signaling Pathways Involved in the Regulation of mRNA Translation DOI Creative Commons
Philippe P. Roux, Ivan Topisirović

Molecular and Cellular Biology, Journal Year: 2018, Volume and Issue: 38(12)

Published: April 3, 2018

Translation is a key step in the regulation of gene expression and one most energy-consuming processes cell. In response to various stimuli, multiple signaling pathways converge on translational machinery regulate its function. To date, roles phosphoinositide 3-kinase (PI3K)/AKT mitogen-activated protein kinase (MAPK) translation are among best understood. Both engage mechanistic target rapamycin (mTOR) variety components machinery. While these synthesis homeostasis, their dysregulation results aberrant leading human diseases, including diabetes, neurological disorders, cancer. Here we review PI3K/AKT MAPK mRNA translation. We also highlight additional mechanisms that have recently emerged as regulators apparatus.

Language: Английский

Citations

285

mTOR substrate phosphorylation in growth control DOI Creative Commons
Stefania Battaglioni, Don Benjamin, Matthias Wälchli

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(11), P. 1814 - 1836

Published: May 1, 2022

Language: Английский

Citations

278

mTORC1 and SIRT1 Cooperate to Foster Expansion of Gut Adult Stem Cells during Calorie Restriction DOI Creative Commons
Masaki Igarashi, Leonard Guarente

Cell, Journal Year: 2016, Volume and Issue: 166(2), P. 436 - 450

Published: June 25, 2016

Language: Английский

Citations

273

The S6K protein family in health and disease DOI
Mariana Tavares, Isadora Carolina Betim Pavan,

Camila Libardi do Amaral

et al.

Life Sciences, Journal Year: 2015, Volume and Issue: 131, P. 1 - 10

Published: April 6, 2015

Language: Английский

Citations

225

Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development DOI Creative Commons

Mayur Vilas Jain,

Anna Paczulla,

Thomas Klonisch

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2013, Volume and Issue: 17(1), P. 12 - 29

Published: Jan. 1, 2013

Summary The rapid accumulation of knowledge on apoptosis regulation in the 1990s was followed by development several experimental anticancer‐ and anti‐ischaemia (stroke or myocardial infarction) drugs. Activation apoptotic pathways removal cellular inhibitors has been suggested to aid cancer therapy inhibition thought limit ischaemia‐induced damage. However, initial clinical studies apoptosis‐modulating drugs led unexpected results different conditions this may have due co‐effects non‐apoptotic interconnected cell death mechanisms ‘yin‐yang’ role autophagy survival versus death. In review, we extend analysis beyond apoptosis. Upon introduction molecular governing necrosis (also called necroptosis programmed necrosis), focus character signals shared processes involving mitochondria ( e.g . mitophagy mitoptosis) playing prominent roles multiple Bcl2‐family members p53). We also briefly highlight stress‐induced senescence that plays a not only organismal ageing but offers novel anticancer strategies. Finally, illustrate forms settings while discussing irradiation‐induced mitotic catastrophe. signalling are discussed their relation biology treatment approaches.

Language: Английский

Citations

223

Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition DOI

Aaron Boudreau,

Hans E. Purkey,

A. Hitz

et al.

Nature Chemical Biology, Journal Year: 2016, Volume and Issue: 12(10), P. 779 - 786

Published: Aug. 1, 2016

Language: Английский

Citations

212

AMPK directly activates mTORC2 to promote cell survival during acute energetic stress DOI Open Access
Dubek Kazyken, Brian Magnuson, Çağrı Bodur

et al.

Science Signaling, Journal Year: 2019, Volume and Issue: 12(585)

Published: June 11, 2019

AMP-activated protein kinase (AMPK) senses energetic stress and, in turn, promotes catabolic and suppresses anabolic metabolism coordinately to restore energy balance. We found that a diverse array of AMPK activators increased mTOR complex 2 (mTORC2) signaling an AMPK-dependent manner cultured cells. Activation with the type diabetes drug metformin (GlucoPhage) also mTORC2 liver vivo primary hepatocytes manner. AMPK-mediated activation did not result from suppression mTORC1 thus reduced negative feedback on PI3K flux. Rather, associated directly phosphorylated (mTOR rictor). As determined by two-stage vitro assay, phosphorylation recombinant was sufficient increase catalytic activity toward Akt. Hence, components downstream signaling. Functionally, inactivation AMPK, mTORC2, Akt apoptosis during acute stress. By showing activates cell survival, these data provide potential mechanism for how paradoxically tumorigenesis certain contexts despite its tumor-suppressive function through inhibition growth-promoting mTORC1. Collectively, unveil as target AMPK-mTORC2 axis promoter survival

Language: Английский

Citations

199

Abnormal mTOR Activation in Autism DOI
Kellen D. Winden, Darius Ebrahimi‐Fakhari, Mustafa Şahin

et al.

Annual Review of Neuroscience, Journal Year: 2018, Volume and Issue: 41(1), P. 1 - 23

Published: Feb. 28, 2018

The mechanistic target of rapamycin (mTOR) is an important signaling hub that integrates environmental information regarding energy availability and stimulates anabolic molecular processes cell growth. Abnormalities in this pathway have been identified several syndromes which autism spectrum disorder (ASD) highly prevalent. Several studies investigated mTOR developmental neuronal that, when dysregulated, could contribute to the development ASD. Although many potential mechanisms still remain be fully understood, these associations are great interest because clinical inhibitors. Clinical trials evaluating efficacy inhibitors improve neurodevelopmental outcomes initiated.

Language: Английский

Citations

192

The unique biology of germinal center B cells DOI Creative Commons
Clara Young, Robert Brink

Immunity, Journal Year: 2021, Volume and Issue: 54(8), P. 1652 - 1664

Published: Aug. 1, 2021

Language: Английский

Citations

151

The Hallmarks of Flavonoids in Cancer DOI Creative Commons
Luis Gustavo Saboia Ponte, Isadora Carolina Betim Pavan, Mariana Camargo Silva Mancini

et al.

Molecules, Journal Year: 2021, Volume and Issue: 26(7), P. 2029 - 2029

Published: April 2, 2021

Flavonoids represent an important group of bioactive compounds derived from plant-based foods and beverages with known biological activity in cells. From the modulation inflammation to inhibition cell proliferation, flavonoids have been described as therapeutic adjuvants against several diseases, including diabetes, arteriosclerosis, neurological disorders, cancer. Cancer is a complex multifactor disease that has studied for years however, its prevention still one best efficient factors impacting epidemiology disease. In molecular cellular context, some mechanisms underlying oncogenesis progression are understood, hallmarks this text, we review signaling pathways, inflammation, immunity, redox metabolism, growth, autophagy, apoptosis, cycle, analyze action The current literature provides enough evidence supporting may be cancer therapy, highlighting importance healthy balanced diets prevent onset

Language: Английский

Citations

117