MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3β expression

Jiang, J-J; Cm, Liu; Zhang, BY; Wang, Xue-Wei; Zhang, M; Saijilafu,; Zhang, S-R; Hall, Phil; Hu, Y-W; Zhou, F.F.

doi:10.1038/cddis.2015.239

Cited by 71 publications

(64 citation statements)

References 27 publications

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“…The evidence suggested that miR-26a-5p activity may have a compartmentalized response which would operate differently for the outgrowth of dendrites and axons. For instance, increased miR-26a-5p enhanced axon outgrowth in hippocampal neurons and axon regeneration in the peripheral nervous system [44], [62]. Interestingly, this dual cell response is also observed after decreasing GSK3 (a validated miR-26a-5p target) activity in hippocampal neurons [63].…”

Section: A Role For Sevs In Tranferring Glial Mirnas To Neurons and Tmentioning

confidence: 96%

“…To validate miR-26a-5p activity in the regulation of neuronal morphology, we analyzed the protein levels of its validated target gene products Microtubule Associated Protein 2 (MAP2) [43] and Glycogen Synthase Kinase 3  (GSK3) [44], which also play a key function in neuronal morphology [45], [46]. For this, we evaluated by Western blot the protein levels of MAP2 and GSK3 in hippocampal neurons magnetofected either with a scrambled control nucleotide sequence, a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) or an inhibitor nucleotide sequence targeting miRNA-26a-5p (antago 26a-5p) for 72 hours.…”

Section: Astrocyte-derived Sevs Carry Mir-26-5p Which Targets Gene Ementioning

confidence: 99%

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Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

Luarte¹,

Henzi²,

Fernández³

et al. 2020

Preprint

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In the last decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) which are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e. GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation and also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.Here, we showed that cultured astrocytes that express GFP-tagged Aldo C (Aldo C-GFP) transfer the derived sEVs, carrying the recombinant protein, in order to develop hippocampal neurons, impacting on their dendritic complexity. Using bioinformatics combined with biochemical and molecular approaches, we postulated and then confirmed that the content of miRNA-26a-5 is regulated in Aldo C-GFP-electroporated astrocytes and their sEVs. Finally, we showed that the miRNA-26a-5p-carried by Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) actively regulate the expression of some relevant neuronal proteins for morphogenesis and dendritic complexity. Our results show that sEVs from astrocytes can regulate dendritic complexity depending on the activity of miRNA-26a-5p.. Preprints (www.preprints.org) | NOT PEER-REVIEWED |

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Section: A Role For Sevs In Tranferring Glial Mirnas To Neurons and Tmentioning

confidence: 96%

Section: Astrocyte-derived Sevs Carry Mir-26-5p Which Targets Gene Ementioning

confidence: 99%

Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

Luarte¹,

Henzi²,

Fernández³

et al. 2020

Preprint

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“…The expression of GSK3β can be decreased via expression of miR-26a, leading to promotion of neuronal axon regeneration through gene regulation (Jiang et al, 2015). By inhibiting the proliferation of axons, miR-26 represents a case of gene regulation leading to accelerated aging.…”

Section: Mirna Synthesis/actionmentioning

confidence: 99%

Are microRNAs true sensors of ageing and cellular senescence?

Williams

Smith

Kumar

et al. 2017

Ageing Research Reviews

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All living beings are programmed to death due to aging and age-related processes. Aging is a normal process of every living species. While all cells are inevitably progressing towards death, many disease processes accelerate the aging process, leading to senescence. Pathologies such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, cardiovascular disease, cancer, and skin diseases have been associated with deregulated aging. Healthy aging can delay onset of all age-related diseases. Genetics and epigenetics are reported to play large roles in accelerating and/or delaying the onset of age-related diseases. Cellular mechanisms of aging and age-related diseases are not completely understood. However, recent molecular biology discoveries have revealed that microRNAs (miRNAs) are potential sensors of aging and cellular senescence. Due to miRNAs capability to bind to the 3’ untranslated region (UTR) of mRNA of specific genes, miRNAs can prevent the translation of specific genes. The purpose of our article is to highlight recent advancements in miRNAs and their involvement in cellular changes in aging and senescence. Our article discusses the current understanding of cellular senescence, its interplay with miRNAs regulation, and how they both contribute to disease processes.

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“…In our recently published research, we found that miR-26a promotes axon regeneration by suppressing GSK3 β expression in mammals [92]. In retinal ganglion cells, miR-30b has been proved to promote axon outgrowth by inhibiting the expression of semaphorin 3A (Sema3A), which is a major inhibitory factor of optic nerve (ON) regeneration after injury [93].…”

Section: Micrornas and Intrinsic Determinants Of Axon Regenerationmentioning

confidence: 99%

Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury

Teng

Liu

2016

Neural Plasticity

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Spinal cord injury is a devastating disease which disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. Most injured neurons fail to regenerate in the central nervous system after injury. Multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration after injury. MicroRNAs can modulate multiple genes' expression and are tightly controlled during nerve development or the injury process. Evidence has demonstrated that microRNAs and their signaling pathways play important roles in mediating axon regeneration and glial scar formation after spinal cord injury. This article reviews the role and mechanism of differentially expressed microRNAs in regulating axon regeneration and glial scar formation after spinal cord injury, as well as their therapeutic potential for promoting axonal regeneration and repair of the injured spinal cord.

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MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3β expression

Cited by 71 publications

References 27 publications

Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

Are microRNAs true sensors of ageing and cellular senescence?

Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury

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