MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration.

Autor: Winkler I; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Engler JB; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Vieira V; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Bauer S; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Liu YH; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan., Di Liberto G; Department of Pathology and Immunology, Division of Clinical Pathology, Geneva Faculty of Medicine, University of Geneva and University Hospital of Geneva, Geneva 1211, Switzerland., Grochowska KM; Leibniz Group 'Dendritic Organelles and Synaptic Function', Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany.; Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg 39118, Germany., Wagner I; Department of Pathology and Immunology, Division of Clinical Pathology, Geneva Faculty of Medicine, University of Geneva and University Hospital of Geneva, Geneva 1211, Switzerland., Bier J; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Bal LC; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Rothammer N; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Meurs N; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Egervari K; Department of Pathology and Immunology, Division of Clinical Pathology, Geneva Faculty of Medicine, University of Geneva and University Hospital of Geneva, Geneva 1211, Switzerland., Schattling B; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany., Salinas G; Institut of Human Genetics, NGS Integrative Genomics, University Medical Center Göttingen, Göttingen 37077, Germany., Kreutz MR; Leibniz Group 'Dendritic Organelles and Synaptic Function', Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany.; Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg 39118, Germany., Huang YS; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan., Pless O; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Hamburg 22525, Germany., Merkler D; Department of Pathology and Immunology, Division of Clinical Pathology, Geneva Faculty of Medicine, University of Geneva and University Hospital of Geneva, Geneva 1211, Switzerland., Friese MA; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Nov 24; Vol. 9 (47), pp. eadi6855. Date of Electronic Publication: 2023 Nov 24.
DOI: 10.1126/sciadv.adi6855
Abstrakt: Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA-mRNA network of inflamed motor neurons by leveraging cell type-specific miRNA and mRNA sequencing of mice undergoing experimental autoimmune encephalomyelitis (EAE). We found robust induction of miR-92a in inflamed spinal cord neurons and identified cytoplasmic polyadenylation element-binding protein 3 ( Cpeb3 ) as a key target of miR-92a-mediated posttranscriptional silencing. We detected CPEB3 repression in inflamed neurons in murine EAE and human MS. Moreover, both miR-92a delivery and Cpeb3 deletion protected neuronal cultures against excitotoxicity. Supporting a detrimental effect of Cpeb3 in vivo, neuron-specific deletion in conditional Cpeb3 knockout animals led to reduced inflammation-induced clinical disability in EAE. Together, we identified a neuroprotective miR-92a- Cpeb3 axis in neuroinflammation that might serve as potential treatment target to limit inflammation-induced neuronal damage.
Databáze: MEDLINE