ArticleCell reports2015
The Regulatory Machinery of Neurodegeneration in In Vitro Models of Amyotrophic Lateral Sclerosis.
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Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
4.2field-weighted citation impact, top 6% of its field
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33 citing papers in PubMed, 54 citations in OpenAlex.
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- Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Cells · 2023Review
- Mature iPSC-derived astrocytes of an ALS/FTD patient carrying the TDP43Frontiers in cell and developmental biology · 2023Article
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- Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons.Stem cell reports · 2021Article
- Non-cell-autonomous pathogenic mechanisms in amyotrophic lateral sclerosis.Trends in neurosciences · 2021Review
- Mast Cell and Astrocyte Hemichannels and Their Role in Alzheimer's Disease, ALS, and Harmful Stress Conditions.International journal of molecular sciences · 2021Review
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- Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow.Nature communications · 2020Article
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- TDP-43 enhances translation of specific mRNAs linked to neurodegenerative disease.Nucleic acids research · 2019Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Burcin IkizProgram in Neurobiology and Behavior, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Mariano J AlvarezCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.
Diane B RéCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Virginia Le VercheCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Kristin PolitiCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Program in Pathobiology and Molecular Medicine, Columbia University, New York, NY 10032, USA.
Francesco LottiCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Sudarshan PhaniCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Radhika PradhanCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Changhao YuCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Gist F CroftProgram in Neurobiology and Behavior, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Department of Rehabilitation and Regenerative Medicine and Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University, New York, NY 10032, USA.
Arnaud JacquierCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Christopher E HendersonProgram in Neurobiology and Behavior, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Department of Rehabilitation and Regenerative Medicine and Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Columbia University, New York, NY 10032, USA.
Andrea CalifanoCenter for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, 10032, USA. Electronic address: califano@c2b2.columbia.edu.
Serge PrzedborskiProgram in Neurobiology and Behavior, Columbia University, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative and Columbia Translational Neuroscience Initiative, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Program in Pathobiology and Molecular Medicine, Columbia University, New York, NY 10032, USA; Department of Neurology, Columbia University, New York, NY 10032, USA. Electronic address: sp30@columbia.edu.
Columbia University · USColumbia University Irving Medical Center · US
Funding
True Metal fac coreP30ES009089 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MATTHEW S PERZANOWSKI · 1998 to 2026
$44.7MNation Center: Multi-Scale Study- Cellular Networks(RMI)U54CA121852 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2005 to 2015
$37.4MMitochondria quality control in SOD1-ALSR01NS062055 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI MANFREDI, GIOVANNI · 2009 to 2019
$3.7MProinflammatory enzymes in amytrophic lateral sclerosisR01NS042269 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2001 to 2012
$3.0MHigh-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0MRole of MMP-9 in selective motor neuron degeneration in ALSR01NS072428 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2013 to 2017
$1.7MPre-clinical testing of necrostatin as a potential small molecule for the treatmeR21NS072182 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2011 to 2012
$441kSignaling pathways of necroptosisR21NS088009 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2014 to 2015
$440kEvaluating HMG-CoA reductase as a therapeutic target in ALSR21NS078614 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2013 to 2014
$438kNCI NIH HHS 5U54CA121852-08NCI NIH HHS U54 CA121852NIEHS NIH HHS NIEHS ES009089NIEHS NIH HHS P30 ES009089NIH HHS S10 OD012351NINDS NIH HHS NS042269-05A2NINDS NIH HHS NS062055-03NINDS NIH HHS NS072182-01NINDS NIH HHS NS072428-04NINDS NIH HHS NS078614-02NINDS NIH HHS NS088009-02NINDS NIH HHS R01 NS042269NINDS NIH HHS R01 NS062055NINDS NIH HHS R01 NS072428NINDS NIH HHS R21 NS072182NINDS NIH HHS R21 NS078614NINDS NIH HHS R21 NS088009
Abstract
Neurodegenerative phenotypes reflect complex, time-dependent molecular processes whose elucidation may reveal neuronal class-specific therapeutic targets. The current focus in neurodegeneration has been on individual genes and pathways. In contrast, we assembled a genome-wide regulatory model (henceforth, "interactome"), whose unbiased interrogation revealed 23 candidate causal master regulators of neurodegeneration in an in vitro model of amyotrophic lateral sclerosis (ALS), characterized by a loss of spinal motor neurons (MNs). Of these, eight were confirmed as specific MN death drivers in our model of familial ALS, including NF-κB, which has long been considered a pro-survival factor. Through an extensive array of molecular, pharmacological, and biochemical approaches, we have confirmed that neuronal NF-κB drives the degeneration of MNs in both familial and sporadic models of ALS, thus providing proof of principle that regulatory network analysis is a valuable tool for studying cell-specific mechanisms of neurodegeneration.
Indexed as
Models, BiologicalAmyotrophic Lateral SclerosisAnimalsApoptosisAstrocytesCells, CulturedCulture Media, ConditionedHomeodomain ProteinsHumansMiceMice, TransgenicMotor NeuronsMutationNF-kappa BRNA InterferenceRNA, Small InterferingCulture Media, ConditionedHb9 protein, mouseHomeodomain ProteinsNF-kappa BRNA, Small InterferingSuperoxide DismutaseTranscription Factors
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