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

The clinical translation is hindered by unstandardized protocols, flawed cooling devices, and incomplete understanding of human brown adipose tissue function. Further research is necessary to elucidate these risks and develop strategies balancing the benefits and harms of cold exposure for clinical translation.

Therefore, our findings support NaV1.8 and TRPV1 as important therapeutic targets for alleviating or preventing neuropathic symptoms induced by paclitaxel. Additionally, these results validate the application of long-term nociceptor primary cultures as preclinical models to investigate the cumulative neurotoxicity of chemotherapeutic agents, as well as to evaluate interventions that promote axonal regeneration and decrease hyperexcitability.

Whereas the PL-based probe labeled many established covalent and noncovalent PL targets (e.g., GSTP1, GSTO1, STAT3, and KEAP1), no off-targets were detected for HKC22, suggesting high selectivity for TRPV2. Finally, PL derivatives inhibited cancer cell migration in vitro and suppressed metastasis in vivo, underscoring the therapeutic potential of selective TRPV2 antagonists.

TMR was superior to RPNI variants and NIM in preventing neuroma formation and alleviating neuropathic pain in this animal model. These findings support TMR as a promising surgical strategy to mitigate post-amputation neuroma pain.

In a sciatic nerve ligation model, GelMAMAVP MPs system demonstrated markedly superior analgesic efficacy over the conventional VEGFR2 inhibitor vandetanib...Furthermore, GelMAMAVP MPs distributed in the peripheral nerve stumps indirectly downregulated pain-related proteins (TRPA1/CGRP) in dorsal root ganglia and suppressed spinal microglial activation. Overall, this study presents a comprehensive and safe vascular-targeted strategy promoting nerve end interface self-resolution and prevention of neuropathic pain.

Our findings provide mechanistic insights into the reciprocal TRPA1-TLR2 signaling pathway in α-syn-induced astrocyte pathology and underscore the disease-modifying potential of focused transcranial ULIUSm on astrocytes for the treatment of LBD. This study establishes a novel therapeutic strategy to alleviate neuroinflammation and cognitive decline associated with LBD. The demonstration of its long-term safety further supports ULIUS as a promising therapeutic strategy.

In mouse xenograft models, PANX1 knockdown suppressed, whereas PANX1 overexpression enhanced, tumor growth in vivo. These findings indicate that SCLC exploits a PANX1-dependent ATP release mechanism to engage P2RX7-mediated autocrine signaling and suggest that targeting this axis may represent a potential therapeutic opportunity for this lethal cancer.

In addition, co-immunoprecipitation experiments, coupled to gene silencing approaches, highlighted the cation channel TRPA1 as a potential contributor to FGFR2c oncogenic signaling by regulating its recruitment to cholesterol-enriched signaling platforms. Overall, our findings indicate that FGFR2c, TRPA1 and lipid raft components represent promising targets for the development of novel cancer type-specific therapeutic strategies.

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.