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Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE253840 | GEO | 2024/02/20

REPOSITORIES: GEO

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Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo [bulkRNA-seq]

Project description:Nuclear factor erythroid 2 like (Nfe2l) gene family members 1-3 mediate cellular response to oxidative stress, including in the central nervous system (CNS). However, neuronal functions of Nfe2l3 are unknown. Here, we comparatively evaluated expression of Nfe2l1, Nfe2l2, and Nfe2l3 in singe cell RNA-seq (scRNA-seq)-profiled cortical and retinal ganglion cell (RGC) CNS projection neurons, investigated whether Nfe2l3 regulates neuroprotection and axon regeneration after CNS injury in vivo, and characterized a gene network associated with Nfe2l3 in neurons. We showed that, Nfe2l3 expression transiently peaks in developing immature cortical and RGC projection neurons, but is nearly abolished in adult neurons and is not upregulated after injury. Furthermore, within the retina, Nfe2l3 is enriched in RGCs, whereas Nfe2l1 and Nfe2l2 are expressed robustly in other retinal cell types as well, and are also upregulated after injury. We also found that, expressing Nfe2l3 in injured RGCs through localized intralocular viral vector delivery promotes neuroprotection and long-distance axon regeneration after optic nerve injury in vivo. Moreover, Nfe2l3 treatment provided a similar extent of neuroprotection and axon regeneration as viral vector-targeting of Pten and Klf9, which are prominent regulators of neuroprotection and long-distance axon regeneration. Finally, we bioinformatically characterized a gene network associated with Nfe2l3 in neurons, which revealed the association of Nfe2l3 with established mechanisms of neuroprotection and axon regeneration. Thus, Nfe2l3 is a novel neuroprotection and axon regeneration-promoting factor with a therapeutic potential for treating CNS injury and disease.

2024-02-22 | GSE253838 | GEO

Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo [Third party: scRNA-seq]

2024-02-22 | GSE253839 | GEO

Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo

Project description:Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo

| PRJNA1067542 | ENA

Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo [bulkRNA-seq]

Project description:Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo [bulkRNA-seq]

| PRJNA1067544 | ENA

Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-01-26 | GSE252517 | GEO

Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo [RNA-seq]

Project description:Numerous micro-RNAs (miRNAs) affect neurodevelopment and neuroprotection, but potential roles of many miRNAs in regulating these processes are still unknown. Here, we used the retinal ganglion cell (RGC) central nervous system (CNS) projection neuron and optic nerve crush (ONC) injury model, to optimize a mature miRNA arm-specific quantification method for characterizing the developmental regulation of miR-1247-5p in RGCs, investigated whether injury affects its expression, and tested whether upregulating miR-1247-5p-mimic in RGCs promotes neuroprotection and axon regeneration. We found that, miR-1247-5p is developmentally-downregulated in RGCs, and is also further downregulated after ONC. Importantly, RGC-specific upregulation of miR-1247-5p promoted neuroprotection and axon regeneration after injury in vivo. To gain insight into the underlying mechanisms, we analyzed by bulk-mRNA-seq embryonic and adult RGCs, along with adult RGCs transduced by miR-1247-5p-expressing viral vector, and identified developmentally-regulated cilial and mitochondrial biological processes, which were reinstated to their embryonic levels in adult RGCs by upregulation of miR-1247-5p. Because axon growth is also a developmentally-regulated process, in which mitochondrial dynamics play important roles, it is possible that miR-1247-5p promoted neuroprotection and axon regeneration through regulating mitochondrial functions.

2024-01-26 | GSE252514 | GEO

Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury.

Project description:Optic nerve injury induces optic nerve degeneration and retinal ganglion cell (RGC) death that lead to visual disturbance. In this study, we examined if topical ripasudil has therapeutic potential in adult mice after optic nerve crush (ONC). Topical ripasudil suppressed ONC-induced phosphorylation of p38 mitogen-activated protein kinase and ameliorated RGC death. In addition, topical ripasudil significantly suppressed the phosphorylation of collapsin response mediator protein 2 and cofilin, and promoted optic nerve regeneration. These results suggest that topical ripasudil promotes RGC protection and optic nerve regeneration by modulating multiple signaling pathways associated with neural cell death, microtubule assembly and actin polymerization.

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Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo [Small-RNA-seq]

2024-01-26 | GSE252516 | GEO

Experimental upregulation of developmentally downregulated ribosomal protein large subunits 7 and 7A promotes axon regeneration after injury in vivo

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-28 | GSE240317 | GEO

Augmenting fibronectin levels in injured adult CNS promotes axon regeneration in vivo

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-06-28 | GSE269816 | GEO