PGC1α: an emerging therapeutic target for chemotherapy-induced peripheral neuropathy

Zhai, Mingzhu; Hu, Haibei; Zheng, Yi; Wu, Benqing; Sun, Wuping

doi:10.1177/17562864231163361

Cited by 5 publications

(2 citation statements)

References 92 publications

(120 reference statements)

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“…U The ubiquitin proteasome system and microtubules are recognized as master regulators of central and peripheral nervous system axon degeneration [30]. Furthermore, mitochondrial damage and oxidative stress are well-documented events in CIPN [8,31]. Additionally, gene set enrichment analysis (GSEA) indicated an increase in interleukin 17 production in C_LTMR neurons after exposure to paclitaxel.…”

Section: Gene Interaction Analysis Unveiled Gene Modules Associated W...mentioning

confidence: 99%

Single-Nuclei RNA Sequencing Identifies Type C Low-Threshold Mechanoreceptors as Key Players in Paclitaxel-Induced Peripheral Neuropathy

Sun,

Li,

Zhang

et al. 2024

Preprint

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Neuropathic pain triggered by chemotherapy poses a significant clinical challenge. Investigating cell type-specific alterations through single-cell transcriptome analysis holds promise in understanding symptom development and pathogenesis. In this study, we performed single nuclei RNA (snRNA) sequencing of dorsal root ganglions (DRG) to explore the molecular mechanism underlying paclitaxel-induced neuropathic pain. Mouse exposed to repeated paclitaxel doses developed persistent pain hypersensitivity lasting at least 21 days. The snRNA sequencing unveiled seven major cell types within DRGs, with neurons further subdivided into 12 distinct subclusters using known markers. Notably, type C low-threshold mechanoreceptors (C_LTMR) exhibited the most pronounced transcriptomic changes post-paclitaxel administration. Differential gene expression and Gene Ontology (GO) analysis highlighted suppressed potassium-related currents, microtubule transport, and mitochondrial functions in C_LTMR following paclitaxel treatment. Meanwhile, Gene Set Enrichment Analysis (GSEA) suggested increased Interleukin 17 production in C_LTMR after paclitaxel exposure. Pseudo-time analysis uncovered nine distinct states (state 1 to 9) of C_LTMR. State 1 exhibits higher prevalence in paclitaxel-treated mice and altered neurotransmission properties, likely contributing to paclitaxel-induced pain hypersensitivity. This comprehensive exploration sheds light on the molecular mechanisms driving paclitaxel-induced neuropathic pain, offering potential avenues for therapeutic intervention.

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Section: Gene Interaction Analysis Unveiled Gene Modules Associated W...mentioning

confidence: 99%

Single-Nuclei RNA Sequencing Identifies Type C Low-Threshold Mechanoreceptors as Key Players in Paclitaxel-Induced Peripheral Neuropathy

Sun,

Li,

Zhang

et al. 2024

Preprint

Self Cite

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“…Therefore, oxidative stress and dysfunction in mitochondrial and other organelles are important factors in the pathogenesis of CIPN, and they could be potential targets for prevention and treatment strategies. Some of the proposed interventions include antioxidants, mitochondrial modulators, and anti-inflammatory agents [86][87][88]. However, more studies are necessary to establish the efficacy and safety of these approaches in a clinical setting.…”

Section: Oxidative Stress and Mitochondrial Dysfunction In Cipnmentioning

confidence: 99%

Molecular and Cellular Involvement in CIPN

Kacem,

Cimini,

d’Angelo

et al. 2024

Biomedicines

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Many anti-cancer drugs, such as taxanes, platinum compounds, vinca alkaloids, and proteasome inhibitors, can cause chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a frequent and harmful side effect that affects the sensory, motor, and autonomic nerves, leading to pain, numbness, tingling, weakness, and reduced quality of life. The causes of CIPN are not fully known, but they involve direct nerve damage, oxidative stress, inflammation, DNA damage, microtubule dysfunction, and altered ion channel activity. CIPN is also affected by genetic, epigenetic, and environmental factors that modulate the risk and intensity of nerve damage. Currently, there are no effective treatments or prevention methods for CIPN, and symptom management is mostly symptomatic and palliative. Therefore, there is a high demand for better understanding of the cellular and molecular mechanisms involved in CIPN, as well as the development of new biomarkers and therapeutic targets. This review gives an overview of the current knowledge and challenges in the field of CIPN, focusing on the biological and molecular mechanisms underlying this disorder.

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Amelioration of cisplatin-induced neurodegenerative changes in rats and restoration of mitochondrial biogenesis by 6-bromoindirubin-3′-oxime: The implication of the GSK-3β/PGC1-α axis

Magdy,

Eshra,

Rashed

et al. 2024

Tissue and Cell

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PGC1α: an emerging therapeutic target for chemotherapy-induced peripheral neuropathy

Cited by 5 publications

References 92 publications

Single-Nuclei RNA Sequencing Identifies Type C Low-Threshold Mechanoreceptors as Key Players in Paclitaxel-Induced Peripheral Neuropathy

Single-Nuclei RNA Sequencing Identifies Type C Low-Threshold Mechanoreceptors as Key Players in Paclitaxel-Induced Peripheral Neuropathy

Molecular and Cellular Involvement in CIPN

Amelioration of cisplatin-induced neurodegenerative changes in rats and restoration of mitochondrial biogenesis by 6-bromoindirubin-3′-oxime: The implication of the GSK-3β/PGC1-α axis

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