Emerging roles of toll-like receptor 4 in chemotherapy-induced neurotoxicity

Thura Tun Oo; Wasana Pratchayasakul; Nipon Chattipakorn; Siriporn C Chattipakorn

doi:10.1016/j.neuro.2022.09.006

Emerging roles of toll-like receptor 4 in chemotherapy-induced neurotoxicity

Neurotoxicology. 2022 Dec:93:112-127. doi: 10.1016/j.neuro.2022.09.006. Epub 2022 Sep 21.

Authors

Thura Tun Oo¹, Wasana Pratchayasakul², Nipon Chattipakorn², Siriporn C Chattipakorn³

Affiliations

¹ Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.
² Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.
³ Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Electronic address: scchattipakorn@gmail.com.

PMID: 36152729
DOI: 10.1016/j.neuro.2022.09.006

Abstract

Chemotherapy-induced neurotoxicity is one of the most prevalent side effects in cancer patients and survivors. Cognitive decline and peripheral neuropathy are the most common chemotherapy-induced neurotoxic symptoms. These symptoms lead not only to the limiting of the dose of chemotherapy given to cancer patients, but also have an impact on the quality of life of cancer survivors. Although the exact mechanisms involved in chemotherapy-induced neurotoxicity are still unclear, neuroinflammation is widely regarded as being one of the major causes involved in chemotherapy-induced neurotoxicity. It is known that Toll-like receptor 4 (TLR4) plays a critical role in the inflammatory process, and it has been recently reported that it is associated with chemotherapy-induced neurotoxicity. In this review, we summarize and discuss all available evidence regarding the activation of the TLR4 signaling pathway in various models of chemotherapy-induced neurotoxicity. This review also emphasizes the evidence pertinent to TLR4 inhibition on chemotherapy-induced neurotoxicity in rodent studies. Understanding the role of the TLR4 signaling pathway behind chemotherapy-induced neurotoxicity is crucial for improving treatments and ensuring the long-term survival of cancer patients.

Keywords: Chemotherapy; Cognitive decline; Myeloid differentiation factor 2; Peripheral neuropathy; Toll-like receptor 4.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / toxicity
Humans
Neoplasms* / drug therapy
Neurotoxicity Syndromes* / drug therapy
Peripheral Nervous System Diseases* / chemically induced
Quality of Life
Toll-Like Receptor 4 / metabolism

Substances

Toll-Like Receptor 4
Antineoplastic Agents