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Citations to this article

A TLR/AKT/FoxO3 immune tolerance–like pathway disrupts the repair capacity of oligodendrocyte progenitors
Taasin Srivastava, … , Larry S. Sherman, Stephen A. Back
Taasin Srivastava, … , Larry S. Sherman, Stephen A. Back
Published April 16, 2018
Citation Information: J Clin Invest. 2018;128(5):2025-2041. https://doi.org/10.1172/JCI94158.
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Research Article Inflammation Neuroscience Article has an altmetric score of 99

A TLR/AKT/FoxO3 immune tolerance–like pathway disrupts the repair capacity of oligodendrocyte progenitors

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Abstract

Cerebral white matter injury (WMI) persistently disrupts myelin regeneration by oligodendrocyte progenitor cells (OPCs). We identified a specific bioactive hyaluronan fragment (bHAf) that downregulates myelin gene expression and chronically blocks OPC maturation and myelination via a tolerance-like mechanism that dysregulates pro-myelination signaling via AKT. Desensitization of AKT occurs via TLR4 but not TLR2 or CD44. OPC differentiation was selectively blocked by bHAf in a maturation-dependent fashion at the late OPC (preOL) stage by a noncanonical TLR4/TRIF pathway that induced persistent activation of the FoxO3 transcription factor downstream of AKT. Activated FoxO3 selectively localized to oligodendrocyte lineage cells in white matter lesions from human preterm neonates and adults with multiple sclerosis. FoxO3 constraint of OPC maturation was bHAf dependent, and involved interactions at the FoxO3 and MBP promoters with the chromatin remodeling factor Brg1 and the transcription factor Olig2, which regulate OPC differentiation. WMI has adapted an immune tolerance–like mechanism whereby persistent engagement of TLR4 by bHAf promotes an OPC niche at the expense of myelination by engaging a FoxO3 signaling pathway that chronically constrains OPC differentiation.

Authors

Taasin Srivastava, Parham Diba, Justin M. Dean, Fatima Banine, Daniel Shaver, Matthew Hagen, Xi Gong, Weiping Su, Ben Emery, Daniel L. Marks, Edward N. Harris, Bruce Baggenstoss, Paul H. Weigel, Larry S. Sherman, Stephen A. Back

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 Total
Citations: 4 3 4 4 4 3 3 25
Citation information
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Citations to this article (25)

Title and authors Publication Year
Potential Role of Endoplasmic Reticulum Stress in Modulating Protein Homeostasis in Oligodendrocytes to Improve White Matter Injury in Preterm Infants.
Liu C, Ju R
Molecular Neurobiology 2024
The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing.
Liu Y, Tan Y, Zhang Z, Yi M, Zhu L, Peng W
Translational Neurodegeneration 2024
TSG-6-Mediated Extracellular Matrix Modifications Regulate Hypoxic-Ischemic Brain Injury.
Srivastava T, Nguyen H, Haden G, Diba P, Sowa S, LaNguyen N, Reed-Dustin W, Zhu W, Gong X, Harris EN, Baltan S, Back SA
The Journal of neuroscience : the official journal of the Society for Neuroscience 2024
Distinct chemical structures inhibit the CEMIP hyaluronidase and promote oligodendrocyte progenitor cell maturation
Peters A, Banine F, Yasuhara K, Hoffman A, Basappa, Metri PK, Gunning L, Huffman A, VanCampen J, Shock CC, Back SA, Sherman LS
The Journal of Biological Chemistry 2024
Genetic architecture of the white matter connectome of the human brain
Sha Z, Schijven D, Fisher SE, Francks C
Science Advances 2023
Postischemic Infusion of Apigenin Reduces Seizure Burden in Preterm Fetal Sheep
Cho KH, Hounsell N, McClendon E, Riddle A, Basappa, Dhillon SK, Bennet L, Back S, Sherman LS, Gunn AJ, Dean JM
International journal of molecular sciences 2023
Ferroptosis of microglia in aging human white matter injury
Adeniyi PA, Gong X, MacGregor E, Degener-O\u2019Brien K, McClendon E, Garcia M, Romero O, Russell J, Srivastava T, Miller J, Keene CD, Back SA
Annals of Neurology 2023
Shh and Olig2 sequentially regulate oligodendrocyte differentiation from hiPSCs for the treatment of ischemic stroke
Xu J, Zhao J, Wang R, Zhang Y, Shen L, Xiao Q, Xie Y, Jiang J, Nie Y, Deng W
Theranostics 2022
New insights into the immunologic role of oligodendrocyte lineage cells in demyelination diseases
Li H, Chen Y, Niu J, Yi C
Journal of Biomedical Research 2022
Roles of NG2 Glia in Cerebral Small Vessel Disease.
He Y, Li Z, Shi X, Ding J, Wang X
Neuroscience Bulletin 2022
Prognosis in substance abuse-related acute toxic leukoencephalopathy: A scoping review.
Macchi ZA, Carlisle TC, Filley CM
Journal of the Neurological Sciences 2022
The extracellular matrix as modifier of neuroinflammation and remyelination in multiple sclerosis
S Ghorbani, VW Yong
Brain 2021
Toll-like receptor 2 and 4 antagonism for the treatment of experimental autoimmune encephalomyelitis (EAE)-related pain
AJ Kwilasz, SM Fulgham, JC Duran-Malle, AE Schrama, EH Mitten, LS Todd, HP Patel, TA Larson, MA Clements, KM Harris, ST Litwiler, LO Harvey, SF Maier, RA Chavez, KC Rice, AM Dam, LR Watkins
Brain, Behavior, and Immunity 2021
Identification of miRNAs That Mediate Protective Functions of Anti-Cancer Drugs During White Matter Ischemic Injury
S Baltan, US Sandau, S Brunet, C Bastian, A Tripathi, H Nguyen, H Liu, JA Saugstad, Y Zarnegarnia, R Dutta
ASN NEURO 2021
Akt Regulates Sox10 Expression to Control Oligodendrocyte Differentiation via Phosphorylating FoxO1.
Wang H, Liu M, Ye Z, Zhou C, Bi H, Wang L, Zhang C, Fu H, Shen Y, Yang JJ, Hu Y, Chen G
The Journal of neuroscience : the official journal of the Society for Neuroscience 2021
Targeting the endocannabinoid system: a predictive, preventive, and personalized medicine-directed approach to the management of brain pathologies
V Reddy, D Grogan, M Ahluwalia, ÉL Salles, P Ahluwalia, H Khodadadi, K Alverson, A Nguyen, SP Raju, P Gaur, M Braun, FL Vale, V Costigliola, K Dhandapani, B Baban, K Vaibhav
The EPMA Journal 2020
Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System
A Peters, LS Sherman
International journal of molecular sciences 2020
miRNA profile is altered in a modified EAE mouse model of multiple sclerosis featuring cortical lesions
NS Orefice, O Guillemot-Legris, R Capasso, P Bottemanne, P Hantraye, M Caraglia, G Orefice, M Alhouayek, GG Muccioli
eLife 2020
Connexin Hemichannel Mimetic Peptide Attenuates Cortical Interneuron Loss and Perineuronal Net Disruption Following Cerebral Ischemia in Near-Term Fetal Sheep
P Yang, JO Davidson, TM Fowke, R Galinsky, G Wassink, RN Karunasinghe, JD Prasad, S Ranasinghe, CR Green, L Bennet, AJ Gunn, JM Dean
International journal of molecular sciences 2020
Dysregulation of Hyaluronan Homeostasis During White Matter Injury
T Srivastava, LS Sherman, SA Back
Neurochemical Research 2019
The Influence of Early Nutrition on Brain Growth and Neurodevelopment in Extremely Preterm Babies: A Narrative Review
BE Cormack, JE Harding, SP Miller, FH Bloomfield
Nutrients 2019
A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination
W Su, S Matsumoto, F Banine, T Srivastava, J Dean, S Foster, P Pham, B Hammond, A Peters, KS Girish, KS Rangappa, Basappa, J Jose, JD Hennebold, MJ Murphy, J BennettToomey, SA Back, LS Sherman
Glia 2019
PPARβ/δ: Linking Metabolism to Regeneration
A Magadum, F Engel
International journal of molecular sciences 2018
Antenatal prevention of cerebral palsy and childhood disability: is the impossible possible?: Preventing cerebral palsy & disability
SJ Ellery, M Kelleher, P Grigsby, I Burd, JB Derks, J Hirst, SL Miller, LS Sherman, M Tolcos, DW Walker
The Journal of Physiology 2018
Regenerative Medicine Therapies for Targeting Neuroinflammation After Stroke
O Rajkovic, G Potjewyd, E Pinteaux
Frontiers in neurology 2018

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