TRPA1 (Transient Receptor Potential Cation Channel Subfamily A Member 1)

Our data also provide the first evidence of heat-induced activation of human TRPV2. Considering previous evidence for TRPV2 and TRPC5 expression in the oral cavity and their roles in oral pain and cancer, our findings indicate that these polymodal channels may participate not only in detecting specific astringent compounds, but also in mediating their broader health-related and anesthetic actions.

Instead, tranilast seems to indirectly suppress channel activation by reducing reactive oxygen species (ROS). This refined understanding of how tranilast modulates TRPV2 has important implications for the interpretation of prior and future pharmacological studies targeting TRPV2.

AD-like chronic itch was induced in mice by topical application of MC903 solution (2 nmol in ethanol) on the shaved nape skin once daily for 14 consecutive days...Schematic summary of the main findings illustrating that SPC alleviates chronic itch in AD by inhibiting spinal astrocyte reactivity and pro-inflammatory signaling. Specifically, SPC suppresses the activation of spinal astrocytes in the dorsal horn, reduces the expression of pro-inflammatory mediators, and thereby decreases scratching behavior in AD mice.

Molecular dynamics simulations validated the structural stability of the interaction between 3-MC and PPARA. These findings suggest that 3-MC promotes ccRCC pathogenesis by targeting specific genes.

Furthermore, the analysis of the cytotoxicity of monoterpene analogs of menthol revealed structure-related activity in menthol-induced cytotoxicity. These findings indicate that menthol-induced cytotoxic effects are concentration-dependent and may provide valuable insights into novel therapeutic strategies for lung cancer.

A967079 (10 µM), a selective TRPA1 antagonist, significantly lessened the cytotoxicity caused by PTX. Additionally, PTX causes sensorimotor and cognitive neuropathy, which was reversed by Li+ treatment. These findings suggest that Li+ may act as a neuroprotective agent, preventing neuronal damage caused by PTX via TRPA1 channel pathways.

The synergistic coupling of a TRPA1-mediated cytosolic Ca2+ surge with MCU-driven mitochondrial import establishes a unidirectional Ca2+ gradient, culminating in irreversible mitochondrial Ca2+ overload and potent tumor cell apoptosis. This work not only demonstrates an efficiently spatiotemporal coordination of dual ion-interference pathways for precision targeting but also establishes a versatile framework for organelle specific modulation of pathological ion fluxes in precision oncology.

Importantly, CBD-induced TRPA1 activation sensitized CRC cells to oxaliplatin, triggering apoptotic-not senescent-cell death...Our findings reveal a non-canonical bioelectric-lysosomal axis that links TRPA1 activity to NRF2 destabilization in colorectal cancer. This work expands the understanding of NRF2 proteostasis under sustained oxidative stress and highlights TRPA1 as a tractable redox-modulating target for overcoming chemoresistance.

By integrating insights from molecular biology, pharmacology, and clinical studies, this work underscores the therapeutic potential of targeting TRP channels as a novel approach in oral cancer management. Future research directions include delineating channel-protein interactions and developing selective TRP inhibitors to improve treatment outcomes.

This represents an active research gap which should be addressed, given the role that TRPA1 appears to play in the inflammatory lung milieu and other malignancies. In this review, we outline the current knowledge surrounding the biological roles of TRPA1 in the lung, summarize the existing drug strategies to target this receptor, and discuss the potential for its targeting either as an anticancer strategy or alternatively for its use in pain management for patients suffering from lung cancer.

This study indicated that different risk score groups exhibited different tumor mutation burden, immune microenvironment cell infiltration, immune response, differentially expressed genes, functional characteristics, correlations with immune checkpoint genes, and drug sensitivity. We established a novel ferroptosis-related oxidative stress gene-related model that possesses potential predictive value for prognosis of patients with LUAD, immunotherapy response, and chemotherapeutic drug sensitivity, and indicated its potential applicability in clinical practice.

Moreover, DMI alleviated pain-related behaviors in chronic pain models, including dextran sulfate sodium (DSS)- induced colitis, complete Freund's adjuvant (CFA)-induced inflammatory pain, oxaliplatin-induced neuropathic pain, and bone cancer pain in mice...Together, our findings demonstrate that DMI acts as a novel TRPA1 agonist for attenuating acute and chronic pain, possible through TRPA1 desensitization. Thus, DMI may be further developed as a potential therapeutic strategy for the treatment of acute and chronic pain.