Prokineticin Receptor Inhibition With PC1 Protects Mouse Primary Sensory Neurons From Neurotoxic Effects of Chemotherapeutic Drugs in vitro.

Abstract

Neurotoxicity is a common side effect of chemotherapeutics that often leads to the development of chemotherapy-induced peripheral neuropathy (CIPN). The peptide Prokineticin 2 (PK2) has a key role in experimental models of CIPN and can be considered an insult-inducible endangering mediator. Since primary afferent sensory neurons are highly sensitive to anticancer drugs, giving rise to dysesthesias, the aim of our study was to evaluate the alterations induced by vincristine (VCR) and bortezomib (BTZ) exposure in sensory neuron cultures and the possible preventive effect of blocking PK2 signaling. Both VCR and BTZ induced a concentration-dependent reduction of total neurite length that was prevented by the PK receptor antagonist PC1. Antagonizing the PK system also reduced the upregulation of PK2, PK-R1, TLR4, IL-6, and IL-10 expression induced by chemotherapeutic drugs. In conclusion, inhibition of PK signaling with PC1 prevented the neurotoxic effects of chemotherapeutics, suggesting a promising strategy for neuroprotective therapies against the sensory neuron damage induced by exposure to these drugs.

• Authors: Giorgia Moschetti, Theodora Kalpachidou, Giada Amodeo, Roberta Lattanzi, Paola Sacerdote, Michaela Kress, Silvia Franchi
• Journal: Frontiers in immunology (Front Immunol) Vol. 11 Pg. 2119 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 33072073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Moschetti, Kalpachidou, Amodeo, Lattanzi, Sacerdote, Kress and Franchi.

Chemical References

• Antineoplastic Agents
• Gastrointestinal Hormones
• Nerve Tissue Proteins
• Neuropeptides
• Neuroprotective Agents
• Prok2 protein, mouse
• RNA, Messenger
• Triazines
• Vincristine
• Bortezomib

Topics

• Animals
• Antineoplastic Agents (toxicity)
• Bortezomib (toxicity)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Down-Regulation
• Drug Evaluation, Preclinical
• Gastrointestinal Hormones (antagonists & inhibitors, physiology)
• Gene Expression Regulation (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Nerve Tissue Proteins (antagonists & inhibitors, physiology)
• Neurites (drug effects, ultrastructure)
• Neuroimmunomodulation (drug effects)
• Neuropeptides (antagonists & inhibitors, physiology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Neurotoxicity Syndromes (prevention & control)
• RNA, Messenger (biosynthesis)
• Sensory Receptor Cells (drug effects, physiology, ultrastructure)
• Triazines (pharmacology, therapeutic use)
• Vincristine (toxicity)