JTC-801 alleviates mechanical allodynia in paclitaxel-induced neuropathic pain through the PI3K/Akt pathway

Huang, Jingxiu; Chen, Dongtai; Fang, Yan; Wu, Shaoyong; Kang, Shiyang; Xing, Wei; Zeng, Weian; Xie, Jingdun

doi:10.1016/j.ejphar.2020.173306

Cited by 21 publications

(14 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that the main pathways for these differentially expressed mRNAs in NP were neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway, MAPK signaling pathway, cAMP signaling pathway, and Calcium signaling pathway. A previous study reported that jct-801 relieves paclitaxel-induced neuropathic pain through the PI3K/Akt pathway (34). Our study suggested that differentially expressed mRNAs are involved in NP possibly through regulating the MAPK signaling pathway, which is consistent with a previous study (35).…”

Section: Discussionsupporting

confidence: 92%

Bioinformatics analysis of the regulatory lncRNA-miRNA-mRNA network in patients with neuropathic pain and prediction of potential therapeutics

Zhang¹,

Liu²,

Song³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Neuropathic pain (NP) is the main form of chronic pain, caused by damage to the nervous system and dysfunction. Here, we aimed at exploring the key molecules involved in NP pathogenesis via the identification of its regulatory lncRNA-miRNA-mRNA network.Methods: We downloaded NP-related data from public databases and identified differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs through differential gene expression analysis. The lncRNA and miRNA target predictions were performed and an integration of the three datasets was used for construction of the lncRNA-miRNA-mRNA network. Subsequently, functional enrichment analysis and protein-protein interaction (PPI) analysis were performed to explore the role and the interactions of the mRNAs. The drug prediction was performed based on the mRNAs in the lncRNA-miRNA-mRNA network. Results: A total of 8,251 differentially expressed mRNAs (4,193 upregulated and 4,058 downregulated), 959 differentially expressed miRNAs (455 upregulated and 504 downregulated), 2,848 differentially expressed lncRNAs (1,324 upregulated and 1,524 downregulated) were identified by integrating the results of the three microarray datasets. We found that differentially expressed mRNAs were mainly enriched in blood circulation, metal ion transmembrane transporter activity, and synaptic membrane. The most significant pathway of mRNAs in lncRNA-miRNA-mRNA network were GTPase, cell cycle, and platelet activation. A total of 1,200 drugs were predicted as potential therapeutics for NP based on the regulatory genes.Conclusion: Our study predicted drugs that may be effective for NP based on the NP regulatory network. This information will help further reveal the pathological mechanism of NP and provide more treatment options for NP patients.

show abstract

Section: Discussionsupporting

confidence: 92%

Bioinformatics analysis of the regulatory lncRNA-miRNA-mRNA network in patients with neuropathic pain and prediction of potential therapeutics

Zhang¹,

Liu²,

Song³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, serum levels of IL-6 are elevated in paclitaxeltreated mice and administration of an IL-6 blocking antibody prevents mechanical allodynia and nerve damage [117,148]. Paclitaxel activates the PI3K/Akt pathway and inhibition of PI3K/Akt alleviates mechanical allodynia in paclitaxel-treated rats [149].…”

Section: Inflammatory Mediatorsmentioning

confidence: 99%

Neuro-immune interactions in paclitaxel-induced peripheral neuropathy

et al. 2021

View full text Add to dashboard Cite

Background: Paclitaxel is a taxane-based chemotherapeutic agent used as a treatment in breast cancer. There is no effective prevention or treatment strategy for the most common side effect of peripheral neuropathy. In this manuscript, we reviewed the molecular mechanisms that contribute to paclitaxel-induced peripheral neuropathy (PIPN) with an emphasis on immune-related processes. Methods: A systematic search of the literature was conducted in PubMed, EMBASE and Cochrane Library. The SYRCLE's risk of bias tool was used to assess internal validity. Results: 156 studies conducted with rodent models were included. The risk of bias was high due to unclear methodology. Paclitaxel induces changes in myelinated axons, mitochondrial dysfunction, and mechanical hypersensitivity by affecting ion channels expression and function and facilitating spinal transmission. Paclitaxel-induced inflammatory responses are important contributors to PIPN. Conclusion: Immune-related processes are an important mechanism contributing to PIPN. Studies in humans that validate these mechanistic data are highly needed to facilitate the development of therapeutic strategies.

show abstract

“…The mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways are activated after PTX injection and are actively involved in the establishment of PIPN [ 25 , 26 ]. In this study, we evaluated the effects of CoPP and GYY4137 on the protein levels of p-P38, p-ERK1/2, PI3K, and p-Akt in the prefrontal cortex (PFC) and dorsal root ganglia (DRG), two specific areas sited in the central (CNS) and peripheral (PNS) nervous system implicated in the modulation of nociception and emotional disorders [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

The Beneficial Effects of Heme Oxygenase 1 and Hydrogen Sulfide Activation in the Management of Neuropathic Pain, Anxiety- and Depressive-like Effects of Paclitaxel in Mice

et al. 2022

View full text Add to dashboard Cite

Chemotherapy-induced peripheral neuropathy constitutes an unresolved clinical problem that severely decreases the quality of the patient’s life. It is characterized by somatosensory alterations, including chronic pain, and a high risk of suffering mental disorders such as depression and anxiety. Unfortunately, an effective treatment for this neuropathology is yet to be found. We investigated the therapeutic potential of cobalt protoporphyrin IX (CoPP), a heme oxygenase 1 inducer, and morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137), a slow hydrogen sulfide (H2S) donor, in a preclinical model of paclitaxel (PTX)-induced peripheral neuropathy (PIPN) in mice. At three weeks after PTX injection, we evaluated the effects of the repetitive administration of 5 mg/kg of CoPP and 35 mg/kg of GYY4137 on PTX-induced nociceptive symptoms (mechanical and cold allodynia) and on the associated emotional disturbances (anxiety- and depressive-like behaviors). We also studied the mechanisms that could mediate their therapeutic properties by evaluating the expression of key proteins implicated in the development of nociception, oxidative stress, microglial activation, and apoptosis in prefrontal cortex (PFC) and dorsal root ganglia (DRG) of mice with PIPN. Results demonstrate that CoPP and GYY4137 treatments inhibited both the nociceptive symptomatology and the derived emotional alterations. These actions were mainly mediated through potentiation of antioxidant responses and inhibiting oxidative stress in the DRG and/or PFC of mice with PIPN. Both treatments normalized some plasticity changes and apoptotic reactions, and GYY4137 blocked microglial activation induced by PTX in PFC. In conclusion, this study proposes CoPP and GYY4137 as good candidates for treating neuropathic pain, anxiety- and depressive-like effects of PTX.

show abstract

JTC-801 alleviates mechanical allodynia in paclitaxel-induced neuropathic pain through the PI3K/Akt pathway

Cited by 21 publications

References 38 publications

Bioinformatics analysis of the regulatory lncRNA-miRNA-mRNA network in patients with neuropathic pain and prediction of potential therapeutics

Bioinformatics analysis of the regulatory lncRNA-miRNA-mRNA network in patients with neuropathic pain and prediction of potential therapeutics

Neuro-immune interactions in paclitaxel-induced peripheral neuropathy

The Beneficial Effects of Heme Oxygenase 1 and Hydrogen Sulfide Activation in the Management of Neuropathic Pain, Anxiety- and Depressive-like Effects of Paclitaxel in Mice

Contact Info

Product

Resources

About