MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration
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MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration. / Winkler, Iris; Engler, Jan Broder; Vieira, Vanessa; Bauer, Simone; Liu, Yi-Hsiang; Di Liberto, Giovanni; Grochowska, Katarzyna M; Wagner, Ingrid; Bier, Jasmina; Bal, Lukas C; Rothammer, Nicola; Meurs, Nina; Egervari, Kristof; Schattling, Benjamin; Salinas, Gabriela; Kreutz, Michael R; Huang, Yi-Shuian; Pless, Ole; Merkler, Doron; Friese, Manuel A.
in: SCI ADV, Jahrgang 9, Nr. 47, eadi6855, 24.11.2023.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration
AU - Winkler, Iris
AU - Engler, Jan Broder
AU - Vieira, Vanessa
AU - Bauer, Simone
AU - Liu, Yi-Hsiang
AU - Di Liberto, Giovanni
AU - Grochowska, Katarzyna M
AU - Wagner, Ingrid
AU - Bier, Jasmina
AU - Bal, Lukas C
AU - Rothammer, Nicola
AU - Meurs, Nina
AU - Egervari, Kristof
AU - Schattling, Benjamin
AU - Salinas, Gabriela
AU - Kreutz, Michael R
AU - Huang, Yi-Shuian
AU - Pless, Ole
AU - Merkler, Doron
AU - Friese, Manuel A
PY - 2023/11/24
Y1 - 2023/11/24
N2 - 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.
AB - 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.
KW - Humans
KW - Mice
KW - Animals
KW - MicroRNAs/genetics
KW - Neuroinflammatory Diseases
KW - Encephalomyelitis, Autoimmune, Experimental/genetics
KW - Multiple Sclerosis
KW - Inflammation/genetics
KW - Neurons/metabolism
KW - RNA, Messenger/metabolism
KW - Mice, Inbred C57BL
KW - RNA-Binding Proteins/genetics
U2 - 10.1126/sciadv.adi6855
DO - 10.1126/sciadv.adi6855
M3 - SCORING: Journal article
C2 - 38000031
VL - 9
JO - SCI ADV
JF - SCI ADV
SN - 2375-2548
IS - 47
M1 - eadi6855
ER -