A Network Pharmacology Approach for the Identification of Common Mechanisms of Drug-Induced Peripheral Neuropathy

Guillermo de Anda-Jáuregui, Brett A. McGregor, Kai Guo, Junguk Hur

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Drug-induced peripheral neuropathy is a side effect of a variety of therapeutic agents that can affect therapeutic adherence and lead to regimen modifications, impacting patient quality of life. The molecular mechanisms involved in the development of this condition have yet to be completely described in the literature. We used a computational network pharmacology approach to explore the Connectivity Map, a large collection of transcriptional profiles from drug perturbation experiments to identify common genes affected by peripheral neuropathy-inducing drugs. Consensus profiles for 98 of these drugs were used to construct a drug–gene perturbation network. We identified 27 genes significantly associated with neuropathy-inducing drugs. These genes may have a potential role in the action of neuropathy-inducing drugs. Our results suggest that molecular mechanisms, including alterations in mitochondrial function, microtubule and cytoskeleton function, ion channels, transcriptional regulation including epigenetic mechanisms, signal transduction, and wound healing, may play a critical role in drug-induced peripheral neuropathy.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalCPT: Pharmacometrics and Systems Pharmacology
Volume8
Issue number4
DOIs
StatePublished - Apr 2019

Fingerprint

Pharmacology
Peripheral Nervous System Diseases
Drugs
Genes
Pharmaceutical Preparations
Signal transduction
Gene
Wound Healing
Perturbation
Cytoskeleton
Ions
Transcriptional Regulation
Ion Channels
Microtubules
Quality of Life
Signal Transduction
Epigenomics
Experiments
Connectivity
Therapeutics

ASJC Scopus subject areas

  • Modeling and Simulation
  • Pharmacology (medical)

Cite this

A Network Pharmacology Approach for the Identification of Common Mechanisms of Drug-Induced Peripheral Neuropathy. / de Anda-Jáuregui, Guillermo; McGregor, Brett A.; Guo, Kai; Hur, Junguk.

In: CPT: Pharmacometrics and Systems Pharmacology, Vol. 8, No. 4, 04.2019, p. 211-219.

Research output: Contribution to journalArticle

@article{c9e00c6c5bb44e8890c89792ac403555,
title = "A Network Pharmacology Approach for the Identification of Common Mechanisms of Drug-Induced Peripheral Neuropathy",
abstract = "Drug-induced peripheral neuropathy is a side effect of a variety of therapeutic agents that can affect therapeutic adherence and lead to regimen modifications, impacting patient quality of life. The molecular mechanisms involved in the development of this condition have yet to be completely described in the literature. We used a computational network pharmacology approach to explore the Connectivity Map, a large collection of transcriptional profiles from drug perturbation experiments to identify common genes affected by peripheral neuropathy-inducing drugs. Consensus profiles for 98 of these drugs were used to construct a drug–gene perturbation network. We identified 27 genes significantly associated with neuropathy-inducing drugs. These genes may have a potential role in the action of neuropathy-inducing drugs. Our results suggest that molecular mechanisms, including alterations in mitochondrial function, microtubule and cytoskeleton function, ion channels, transcriptional regulation including epigenetic mechanisms, signal transduction, and wound healing, may play a critical role in drug-induced peripheral neuropathy.",
author = "{de Anda-J{\'a}uregui}, Guillermo and McGregor, {Brett A.} and Kai Guo and Junguk Hur",
year = "2019",
month = "4",
doi = "10.1002/psp4.12383",
language = "English (US)",
volume = "8",
pages = "211--219",
journal = "CPT: Pharmacometrics and Systems Pharmacology",
issn = "2163-8306",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - A Network Pharmacology Approach for the Identification of Common Mechanisms of Drug-Induced Peripheral Neuropathy

AU - de Anda-Jáuregui, Guillermo

AU - McGregor, Brett A.

AU - Guo, Kai

AU - Hur, Junguk

PY - 2019/4

Y1 - 2019/4

N2 - Drug-induced peripheral neuropathy is a side effect of a variety of therapeutic agents that can affect therapeutic adherence and lead to regimen modifications, impacting patient quality of life. The molecular mechanisms involved in the development of this condition have yet to be completely described in the literature. We used a computational network pharmacology approach to explore the Connectivity Map, a large collection of transcriptional profiles from drug perturbation experiments to identify common genes affected by peripheral neuropathy-inducing drugs. Consensus profiles for 98 of these drugs were used to construct a drug–gene perturbation network. We identified 27 genes significantly associated with neuropathy-inducing drugs. These genes may have a potential role in the action of neuropathy-inducing drugs. Our results suggest that molecular mechanisms, including alterations in mitochondrial function, microtubule and cytoskeleton function, ion channels, transcriptional regulation including epigenetic mechanisms, signal transduction, and wound healing, may play a critical role in drug-induced peripheral neuropathy.

AB - Drug-induced peripheral neuropathy is a side effect of a variety of therapeutic agents that can affect therapeutic adherence and lead to regimen modifications, impacting patient quality of life. The molecular mechanisms involved in the development of this condition have yet to be completely described in the literature. We used a computational network pharmacology approach to explore the Connectivity Map, a large collection of transcriptional profiles from drug perturbation experiments to identify common genes affected by peripheral neuropathy-inducing drugs. Consensus profiles for 98 of these drugs were used to construct a drug–gene perturbation network. We identified 27 genes significantly associated with neuropathy-inducing drugs. These genes may have a potential role in the action of neuropathy-inducing drugs. Our results suggest that molecular mechanisms, including alterations in mitochondrial function, microtubule and cytoskeleton function, ion channels, transcriptional regulation including epigenetic mechanisms, signal transduction, and wound healing, may play a critical role in drug-induced peripheral neuropathy.

UR - http://www.scopus.com/inward/record.url?scp=85064841631&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064841631&partnerID=8YFLogxK

U2 - 10.1002/psp4.12383

DO - 10.1002/psp4.12383

M3 - Article

C2 - 30762308

AN - SCOPUS:85064841631

VL - 8

SP - 211

EP - 219

JO - CPT: Pharmacometrics and Systems Pharmacology

JF - CPT: Pharmacometrics and Systems Pharmacology

SN - 2163-8306

IS - 4

ER -