The many faces and functions of β-catenin

The EMBO Journal, Год журнала: 2012, Номер 31(12), С. 2714 - 2736

Опубликована: Май 22, 2012

Язык: Английский

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Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development

Oxidative Medicine and Cellular Longevity, Год журнала: 2019, Номер 2019, С. 1 - 20

Опубликована: Июль 14, 2019

The transcription factor NRF2 (nuclear erythroid 2-related 2) triggers the first line of homeostatic responses against a plethora environmental or endogenous deviations in redox metabolism, proteostasis, inflammation, etc. Therefore, pharmacological activation is promising therapeutic approach for several chronic diseases that are underlined by oxidative stress and such as neurodegenerative, cardiovascular, metabolic diseases. A particular case cancer, where confers survival advantage to constituted tumors, therefore, inhibition desired. This review describes electrophilic nonelectrophilic activators with clinical projection various We also analyze status inhibitors, which at this time provide proof concept blocking activity cancer therapy.

Язык: Английский

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GSK-3 as potential target for therapeutic intervention in cancer

Oncotarget, Год журнала: 2014, Номер 5(10), С. 2881 - 2911

Опубликована: Май 28, 2014

// James A. McCubrey 1 , Linda S. Steelman Fred E. Bertrand 2 Nicole M. Davis Melissa Sokolosky Steve L. Abrams Giuseppe Montalto 3 Antonino B. D’Assoro 4 Massimo Libra 5 Ferdinando Nicoletti Roberta Maestro 6 Jorg Basecke 7,8 Dariusz Rakus 9 Agnieszka Gizak Zoya Demidenko 10 Lucio Cocco 11 Alberto Martelli and Melchiorre Cervello 12 Department of Microbiology Immunology, Brody School Medicine at East Carolina University Greenville, NC, USA Oncology, Brody Biomedical Internal Specialties, Palermo, Italy Medical Mayo Clinic Cancer Center, Rochester, MN, Bio-Medical Sciences, Catania, Experimental Oncology 1, CRO IRCCS, National Institute, Aviano, Pordenone, Italy. 7 Medicine, Göttingen, Germany 8 Sanct-Josef-Hospital Cloppenburg, Hematology Animal Molecular Physiology, Institute Biology, Wroclaw University, Wroclaw, Poland Cell Stress Roswell Park Buffalo, NY, Dipartimento di Scienze Biomediche e Neuromotorie, Università Bologna, Consiglio Nazionale delle Ricerche, Istituto Biomedicina Immunologia Molecolare “Alberto Monroy”, Correspondence: McCubrey, email: Keywords : GSK-3, cancer stem cells, Wnt/beta-catenin, PI3K, Akt, mTOR, Hedgehog, Notch, Targeted Therapy, Therapy Resistance, Mutations, Rapamycin Received April 24, 2014 Accepted May 28, Published Abstract The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified studied in the regulation synthesis. GSK-3 functions a wide range cellular processes. Aberrant activity has been implicated many human pathologies including: bipolar depression, Alzheimer’s disease, Parkinson’s cancer, non-insulin-dependent diabetes mellitus (NIDDM) others. In some cases, suppression by phosphorylation Akt other kinases associated with progression. these tumor suppressor functions. progression stabilizing components beta-catenin complex. situations, oncogenic properties. While inhibitors to have developed, their use remains controversial because ambiguous role development. this review, we will focus on diverse roles that plays various cancers, particular solid tumors. Recently, also generation cells cell types. We discuss how pivotal interacts multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Notch

Язык: Английский

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GSK3 and its interactions with the PI3K/AKT/mTOR signalling network

Advances in Biological Regulation, Год журнала: 2017, Номер 65, С. 5 - 15

Опубликована: Июнь 27, 2017

Язык: Английский

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Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors

Proceedings of the National Academy of Sciences, Год журнала: 2011, Номер 108(20), С. 8299 - 8304

Опубликована: Апрель 27, 2011

Human embryonic stem cells (hESCs) hold enormous promise for regenerative medicine. Typically, hESC-based applications would require their in vitro differentiation into a desirable homogenous cell population. A major challenge of the current hESC paradigm is inability to effectively capture and, long-term, stably expand primitive lineage-specific stem/precursor that retain broad potential more importantly, developmental stage-specific propensity. Here, we report synergistic inhibition glycogen synthase kinase 3 (GSK3), transforming growth factor β (TGF-β), and Notch signaling pathways by small molecules can efficiently convert monolayer cultured hESCs neuroepithelium within 1 wk under chemically defined condition. These neuroepithelia self-renew presence leukemia inhibitory factor, GSK3 inhibitor (CHIR99021), TGF-β receptor (SB431542); high neurogenic responsiveness instructive neural patterning cues toward midbrain hindbrain neuronal subtypes; exhibit vivo integration. Our work uniformly captures maintains from hESCs.

Язык: Английский

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GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS

Frontiers in Molecular Neuroscience, Год журнала: 2011, Номер 4

Опубликована: Янв. 1, 2011

Inhibiting glycogen synthase kinase-3 (GSK-3) activity via pharmacological intervention has become an important strategy for treating neurodegenerative and psychiatric disorders. The known GSK-3 inhibitors are of diverse chemotypes mechanisms action include compounds isolated from natural sources, cations, synthetic small-molecule ATP-competitive inhibitors, non-ATP-competitive substrate-competitive inhibitors. Here we describe the variety with a specific emphasis on their biological activities in neurons neurological We further highlight our current progress development GSK-3. available data raise hope that one or more these drug design approaches will prove successful at stabilizing even reversing aberrant neuropathology cognitive deficits certain central nervous system

Язык: Английский

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Sculpting Neural Circuits by Axon and Dendrite Pruning

Annual Review of Cell and Developmental Biology, Год журнала: 2015, Номер 31(1), С. 779 - 805

Опубликована: Окт. 5, 2015

The assembly of functional neural circuits requires the combined action progressive and regressive events. Regressive events encompass a variety inhibitory developmental processes, including axon dendrite pruning, which facilitate removal exuberant neuronal connections. Most pruning involves axons that had already made synaptic connections; thus, is tightly associated with synapse elimination. In many instances, these processes are regulated by interplay between neurons glial cells act instructively during remodeling. Owing to importance dendritic remodeling require precise spatial temporal control, this achieved range distinct molecular mechanisms. Disruption mechanisms results in abnormal has been linked brain dysfunction. Therefore, understanding will be instrumental advancing our knowledge disease mental disorders.

Язык: Английский

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A Small Molecule Screen in Stem-Cell-Derived Motor Neurons Identifies a Kinase Inhibitor as a Candidate Therapeutic for ALS

Cell stem cell, Год журнала: 2013, Номер 12(6), С. 713 - 726

Опубликована: Апрель 18, 2013

Язык: Английский

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How to make a midbrain dopaminergic neuron

Development, Год журнала: 2015, Номер 142(11), С. 1918 - 1936

Опубликована: Май 26, 2015

ABSTRACT Midbrain dopaminergic (mDA) neuron development has been an intense area of research during recent years. This is due in part to a growing interest regenerative medicine and the hope that treatment for diseases affecting mDA neurons, such as Parkinson's disease (PD), might be facilitated by better understanding how these neurons are specified, differentiated maintained vivo. knowledge help instruct efforts generate vitro, which holds promise not only cell replacement therapy, but also modeling drug discovery. In this Primer, we will focus on developments molecular mechanisms regulate vivo, they have used human vitro from pluripotent stem cells or somatic via direct reprogramming. Current challenges future avenues PD identified discussed.

Язык: Английский

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Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons

Cell stem cell, Год журнала: 2015, Номер 17(6), С. 735 - 747

Опубликована: Окт. 23, 2015

Язык: Английский

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