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.

Identification of Novel Regulators of Zalcitabine-Induced Neuropathic Pain

“…One of the most prevalent adverse effects related to antiretrovirals is neuropathic pain, which is induced by different types of damage in peripheral neurons leading to hypersensitivity. 11 In our work, we aimed to deconvolute the mechanism of this harmful effect, by employing a combination of neuronal functional assays and transcriptomics in an immortalized sensory neuronal cell line. Thus, we exposed differentiating F11 cells to zalcitabine, an antiviral that has been related to the induction of neuropathic pain as an adverse effect.…”

The prevalence, distribution and impact of peripheral neuropathy among Danish patients with cancer – a population-based cross-sectional study

“…Common drugs such as statins can cause PN [38] and antihypertensive drugs and antidiabetic drugs can in uence pathophysiological mechanisms involved in development of CIPN [5,39]. Novel methodologies such as system bioinformatics and machine learning are being employed to adequately capture and operationalize the large datasets of drug-drug/drug-gene interaction to yield new knowledge about drug interactions in PN pathophysiology [40,41].…”

Ferulic Acid and P-Coumaric Acid Synergistically Attenuate Non-Alcoholic Fatty Liver Disease through HDAC1/PPARG-Mediated Free Fatty Acid Uptake

“…With the development of systems biology, network pharmacology emerges [ 15 ], which establishes effective targeted, multi-component therapeutic networks and has become an appropriate method to study biologically active nutrients and their mechanisms [ 16 ]. In this study, the ameliorating effects of FA/p-CA on fatty liver were evaluated by network pharmacology analysis and in vitro and in vivo experiments.…”