ApoA-I binding protein (AIBP) regulates transient receptor potential vanilloid 1 (TRPV1) activity in rat dorsal root ganglion neurons by selective disruption of toll-like receptor 4 (TLR4)-lipid rafts - PubMed (original) (raw)

doi: 10.1016/j.bbi.2024.10.017. Epub 2024 Oct 14.

Megan L Uhelski 1, Robert Y North 2, Luke B Farson 3, Christopher B Bankston 3, Gavin H Roland 3, Dwight H Fan 3, Katherine N Sheffield 4, Amy Jia 5, Dana Orlando 3, Mario Heles 1, Tony L Yaksh 6, Yury I Miller 7, Therese A Kosten 8, Patrick M Dougherty 9

Affiliations

ApoA-I binding protein (AIBP) regulates transient receptor potential vanilloid 1 (TRPV1) activity in rat dorsal root ganglion neurons by selective disruption of toll-like receptor 4 (TLR4)-lipid rafts

Yan Li et al. Brain Behav Immun. 2025 Jan.

Abstract

Toll-like receptor 4 (TLR4) and the transient receptor potential vanilloid subtype 1 (TRPV1) are both upregulated and play key roles in the induction and expression of paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Using Apolipoprotein A-I binding protein, non-specific cholesterol depletion, TLR4 mis-sense rats and a TLR4 inhibitor, we demonstrate that co-localization of TRPV1 with TLR4 to cholesterol-rich lipid membrane rafts in nociceptors is essential for its normal activation as well as for its exaggerated activation that underlies the development and expression of CIPN. The findings suggest that TLR4-lipid rafts may have an essential role in numerous neuroinflammatory and neuropathic pain conditions. This mechanism is also generalized to female rats for the first time.

Keywords: Calcium imaging; Chemotherapy; Neuropathy; Paclitaxel; TLR4 mis-sense; Whole-cell recording.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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