Estrogen improved the regeneration of axons after subcortical axon injury via regulation of PI3K/Akt/CDK5/Tau pathway

Xia, Xiaohui; Zhou, Changlong; Sun, Xiaochuan; He, Xuenong; Liu, Chang; Wang, Guanyu

doi:10.1002/brb3.1777

Cited by 12 publications

(7 citation statements)

References 36 publications

(36 reference statements)

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“…Furthermore, the transmembrane receptor protein tyrosine kinase signaling pathway was significantly enriched, indicating that RTK signaling may be the primary upstream pathway used by the CH02 peptide. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified enrichment in pathways, most of which are involved in regulating axon outgrowth or regeneration, including AMPK 41 and MAPK signaling 14 , 45 - 47 , regulation of actin cytoskeleton 48 , 49 , and calcium 3 , 50 , mammalian target of rapamycin (mTOR) 6 , 51 - 54 , VEGF 55 - 58 , and PI3K-Akt signaling (Figure 6 B) 8 , 59 , 60 . Of note, several of these signaling pathways are directly or indirectly regulated by FGFRs or other RTK signals 22 , 61 - 65 .…”

Section: Resultsmentioning

confidence: 99%

Peptide ligands targeting FGF receptors promote recovery from dorsal root crush injury via AKT/mTOR signaling

Zhao¹,

Wang²,

Xie³

et al. 2021

Theranostics

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Section: Resultsmentioning

confidence: 99%

Peptide ligands targeting FGF receptors promote recovery from dorsal root crush injury via AKT/mTOR signaling

Zhao¹,

Wang²,

Xie³

et al. 2021

Theranostics

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“…This suggests that the kinase phosphorylating tau in a GAS5-dependent manner is not GSK3α/β. Others have shown that AKT and CDK5 47 or MARK 48 mediate tau phosphorylation. Future studies utilizing kinase assays, mutations of phospho sites on tau will be undertaken by us to identify the GAS5-dependent kinase phosphorylating tau in neurons.…”

Section: Discussionmentioning

confidence: 99%

Small molecule targeting long noncoding RNA GAS5 administered intranasally improves neuronal insulin signaling and decreases neuroinflammation in an aged mouse model

Patel

Lui

Moss

et al. 2023

Sci Rep

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Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and Alzheimer’s disease brain. The role and targets of lncRNA GAS5 in the aging brain were elucidated using a GAS5-targeting small molecule NPC86, a frontier in lncRNA-targeting therapeutic. Robust techniques such as molecular dynamics simulation of NPC86 binding to GAS5, in vitro functional assays demonstrating that GAS5 regulates insulin signaling, neuronal survival, phosphorylation of tau, and neuroinflammation via toll-like receptors support the role of GAS5 in maintaining healthy neurons. The study demonstrates the safety and efficacy of intranasal NPC86 treatment in aged mice to improve cellular functions with transcriptomic analysis in response to NPC86. In summary, the study demonstrates that GAS5 contributes to pathways associated with neurodegeneration and NPC86 has tremendous therapeutic potential to prevent the advent of neurodegenerative diseases and dementias.

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“…ERP30 is an ER among membrane receptors ( 19 ). Estrogen activates the PI3K-Akt signaling pathway after binding to the ER ( 22 , 23 ). Furthermore, the PI3K-Akt signaling pathway is one of the pathways that promote cell proliferation ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Electro-Acupuncture Regulates Metabolic Disorders of the Liver and Kidney in Premature Ovarian Failure Mice

Chen

Guo

et al. 2022

Front. Endocrinol.

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As per the theory of traditional Chinese medicine (TCM), the liver and kidney dysfunction are important pathogenies for premature ovarian failure (POF). POF is a common gynecological disease that reduced the pregnancy rate. Electro-acupuncture (EA) is a useful non-pharmaceutical therapy that supposedly regulates the function of the liver and kidney in the treatment of POF with TCM. However, the underlying mechanism of EA in the treatment of POF has not been adequately studied through metabonomics with reference to the theory of TCM. Accordingly, we investigated the effect of EA on the liver and kidney metabolites in POF mice through metabolomics. POF mice were established via intraperitoneal injection of cisplatin. Both Sanyinjiao (SP6) and Guanyuan (CV4) were stimulated by EA for 3 weeks. The biological samples (including the serum and the ovary, liver, and kidney tissues) were evaluated by histopathology, molecular biology, and hydrogen-1 nuclear magnetic resonance (1HNMR)–based metabolomics to assess the efficacy of EA. 1HNMR data were analyzed by the orthogonal partial least squares discriminant analysis (OPLS-DA). The results revealed that EA was beneficial to ovarian function and the menstrual cycle of POF. Both the energy metabolism and neurotransmitter metabolism in the liver and kidney were regulated by EA. Notably, EA played an important role in regulating energy-related metabolism in the kidney, and the better effect of neurotransmitter-related metabolism in the liver was regulated by EA. These findings indicated that the ovarian functions could be improved and the metabolic disorder of the liver and kidney caused by POF could be regulated by EA. Our study results thus suggested that the EA therapy, based on the results for the liver and kidney, were related to POF in TCM, as preliminarily confirmed through metabolomics.

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Estrogen improved the regeneration of axons after subcortical axon injury via regulation of PI3K/Akt/CDK5/Tau pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 12 publications

References 36 publications

Peptide ligands targeting FGF receptors promote recovery from dorsal root crush injury via AKT/mTOR signaling

Peptide ligands targeting FGF receptors promote recovery from dorsal root crush injury via AKT/mTOR signaling

Small molecule targeting long noncoding RNA GAS5 administered intranasally improves neuronal insulin signaling and decreases neuroinflammation in an aged mouse model

Electro-Acupuncture Regulates Metabolic Disorders of the Liver and Kidney in Premature Ovarian Failure Mice

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