Current insights and therapeutic strategies for targeting TRPV1 in neuropathic pain management

Life Sciences, Journal Year: 2024, Volume and Issue: 355, P. 122954 - 122954

Published: Aug. 10, 2024

Neuropathic pain, a common symptom of several disorders, exerts substantial socioeconomic burden worldwide. Transient receptor potential vanilloid 1 (TRPV1), non-selective cation channel predominantly ex-pressed in nociceptive neurons, plays pivotal role nociception, by detecting various endogenous and exogenous stimuli, including heat, pro-inflammatory mediators, physical stressors. Dysregulation TRPV1 signaling further contributes to the pathophysiology neuropathic pain. Therefore, targeting is promising strategy for developing novel analgesics with improved efficacy safety profiles. Several pharmacological approaches modulate activity, agonists, antagonists, biological RNA interference (RNAi, small interfering [siRNA]) have been explored. Despite preclinical success, clinical translation TRPV1-targeted therapies has encountered challenges, hyperthermia, hypothermia, pungency, desensitization. Nevertheless, ongoing research efforts aim refine interventions through structural modifications, development selective modulators, discovery natural, peptide-based drug candidates. Herein, we provide guidance researchers clinicians involved new specifically reviewing existing literature highlighting current activities. This study discusses future endeavors enhancing efficacy, safety, tolerability candidates, thereby facilitates these discoveries into effective alleviate pain disorders.

Language: Английский

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TRPV1 Channels in the Central Nervous System as Drug Targets

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 756 - 756

Published: June 7, 2024

TRPV1 channels are polymodal cation located predominantly on primary afferent neurons that activated by inflammatory mediators, capsaicin (the active component in chili peppers), and noxious heat. channel antagonists potential new analgesic agents, but their development has been hindered the finding they also produce loss of thermal homeostasis response to Results from recent studies indicate it might be possible develop inhibit pain without affecting heat sensation. present central nervous system (CNS) have implicated learning, memory, behaviour. modulators proposed therapeutic treatment neurological psychiatric conditions. However, further understanding role CNS is required before advances neuropsychiatric conditions with can made.

Language: Английский

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TRPV1 channel in the pathophysiology of epilepsy and its potential as a molecular target for the development of new antiseizure drug candidates

Progress in Neurobiology, Journal Year: 2024, Volume and Issue: 240, P. 102634 - 102634

Published: June 2, 2024

Identification of transient receptor potential cation channel, subfamily V member 1 (TRPV1), also known as capsaicin receptor, in 1997 was a milestone achievement the research on temperature sensation and pain signalling. Very soon after it became evident that TRPV1 is implicated wide array physiological processes different peripheral tissues, well central nervous system, thereby could be involved pathophysiology numerous diseases. Increasing evidence suggests modulation may affect seizure susceptibility epilepsy. This channel localized brain regions associated with seizures epilepsy, its overexpression found both animal models samples from epileptic patients. Moreover, non-neuronal cells (microglia, astrocytes, and/or immune cells) have an impact neuroinflammatory play role epilepsy epileptogenesis. In this paper, we provide comprehensive critical overview currently available data possible molecular target for management, trying to identify gaps future directions. Overall, several converging lines implicate potentially attractive but more studies are needed exploit seizures/epilepsy evaluate value ligands candidates new antiseizure drugs.

Language: Английский

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Capsaicin and TRPV1: A Novel Therapeutic Approach to Mitigate Vascular Aging

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

Vascular aging and its associated diseases represent a principal cause of mortality among the global elderly population, making mitigation vascular significant aspiration for humanity. This article explores intersection nature health, focusing on role natural plant, pepper, bioactive compound, capsaicin, in combating aging. By examining molecular cellular mechanisms as well phenotypic alterations blood vessels, we offer comprehensive review effects capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1), within We propose that may serve medication with to slow progress could constitute new strategy treat related disease.

Language: Английский

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Association of TRPV1 and the SIRT3/SOD2 Signaling Pathway in Mononuclear Cells and Astrocyte-Derived Extracellular Vesicles in Patients with Schizophrenia

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 339 - 339

Published: March 25, 2025

Objectives: The transient receptor potential vanilloid type 1 (TRPV1) is a factor that mediates glial cell response with effects on mitochondrial function. It may affect the occurrence and development of schizophrenia. aim this study to further explore schizophrenia biomarkers by analyzing TRPV1 oxidative stress in astrocyte-derived extracellular vesicles (ADEs) peripheral blood mononuclear cells (PBMCs). Methods: A case–control was conducted. Positive Negative Syndrome Scale Brief Assessment Cognition Schizophrenia (BACS) clinical data were obtained from 50 symptomatic patients controls, fasting samples collected for isolation PBMCs ADEs. Western blotting used assess TRPV1, Sirtuin3 (Sirt3), SOD2, acetyl-SOD2. Results: patient group exhibited significantly reduced Sirt3 expression levels ADEs compared control group. In addition, there marked increase SOD2 acetyl-SOD2 levels. negatively correlated negative symptom score showed positive correlations general psychopathology score, positively score. BACS total Conclusion: expressions closely correlated, associated psychiatric symptoms cognitive function indicated could be biomarker reflect disease severity.

Language: Английский

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mosGraphGPT: a foundation model for multi-omic signaling graphs using generative AI

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

Generative pretrained models represent a significant advancement in natural language processing and computer vision, which can generate coherent contextually relevant content based on the pre-training large general datasets fine-tune for specific tasks. Building foundation using scale omic data is promising to decode understand complex signaling patterns within cells. Different from existing of data, we build model,

Language: Английский

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Tet1-mediated activation of the Ampk signaling by Trpv1 DNA hydroxymethylation exerts neuroprotective effects in a rat model of Parkinson’s disease

Functional & Integrative Genomics, Journal Year: 2024, Volume and Issue: 24(5)

Published: Sept. 17, 2024

Language: Английский

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Tubulin interaction at tubulin-binding sequence 1 (TBS1) is required for proper surface expression and TRPV1 channel activity

Life Sciences, Journal Year: 2024, Volume and Issue: 357, P. 123070 - 123070

Published: Sept. 25, 2024

Language: Английский

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