TRPC channels as emerging targets for seizure disorders

Yu, Ying; Li, Wei; Jiang, Jianxiong

doi:10.1016/j.tips.2022.06.007

Cited by 9 publications

(2 citation statements)

References 88 publications

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“…Anti-epileptic drugs (AEDs) are the primary method of therapy for epilepsy, a persistent neurological brain illness affecting about 50 million people worldwide [ 1 , 2 , 3 ]. The proper therapeutic management of AEDs requires monitoring their levels in the blood to ensure efficacy and prevent toxic side effects.…”

Section: Introductionmentioning

confidence: 99%

Disposable Sensor Chips with Molecularly Imprinted Carbon Paste Electrodes for Monitoring Anti-Epileptic Drugs

Aaryashree

Choudhary

Yoshimi

2023

Sensors

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Epilepsy is a neurological disorder that affects millions of people worldwide. Anti-epileptic drugs (AEDs) are critical for their management. However, the therapeutic window is narrow, and traditional laboratory-based therapeutic drug monitoring (TDM) methods can be time consuming and unsuitable for point-of-care testing. To address this issue, we developed a disposable sensor chip based on molecularly imprinted polymer-modified carbon paste electrodes (MIP-CPs) for the TDM of AEDs such as phenobarbital (PB), carbamazepine (CBZ), and levetiracetam (LEV). In this work, functional monomers (methacrylic acid) and crosslinking monomers (methylene bisacrylamide and ethylene glycol dimethacrylate) were copolymerized in the presence of the AED template and grafted on the graphite particles by simple radical photopolymerization. The grafted particles were mixed with silicon oil, dissolving ferrocene as a redox marker to make the MIP-carbon paste (CP). Disposable sensor chips were fabricated by packing the MIP-CP into the base made of poly (ethylene glycol terephthalate) (PET) film. The sensor’s sensitivity was determined using differential pulse voltammetry (DPV), carried out on a single sensor chip for each operation. Linearity was obtained from 0–60 μg/mL in PB and LEV and 0–12 μg/mL in CBZ, covering their respective therapeutic range. The time taken for each measurement was around 2 min. The experiment using whole bovine blood and bovine plasma indicated that the existence of species that interfered had a negligible effect on the test’s sensitivity. This disposable MIP sensor provides a promising approach for point-of-care testing and facilitating the management of epilepsy. Compared with existing tests, this sensor offers a faster and more accurate way to monitor AEDs, which is crucial for optimizing therapy and improving patient outcomes. Overall, the proposed disposable sensor chip based on MIP-CPs represents a significant advancement in AED monitoring, with the potential for rapid, accurate, and convenient point-of-care testing.

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Section: Introductionmentioning

confidence: 99%

Disposable Sensor Chips with Molecularly Imprinted Carbon Paste Electrodes for Monitoring Anti-Epileptic Drugs

Aaryashree

Choudhary

Yoshimi

2023

Sensors

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“…It is rather unfortunate that current medications provide merely symptomatic relief and have not been demonstrated to prevent epilepsy in people at risk or modify the disease progression ( Galanopoulou et al, 2021 ). Therefore, there remains an urgent need for alternative antiepileptic treatments, despite the rapid expansion of modern ASDs that emerged during the first 2 decades of this century ( Varvel et al, 2015 ; Löscher and Klein, 2020 ; Yu et al, 2022 ).…”

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confidence: 99%

Editorial: Neuroinflammation in acquired epilepsy

Jiang

Santhakumar²,

Zhu³

2022

Front. Cell Dev. Biol.

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Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel

Boda,

Yasmen,

Jiang

et al. 2024

Medicinal Research Reviews

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Transient receptor potential canonical 3 (TRPC3) protein belongs to the TRP family of nonselective cation channels. Its activation occurs by signaling through a G protein‐coupled receptor (GPCR) and a phospholipase C‐dependent (PLC) pathway. Perturbations in the expression of TRPC3 are associated with a plethora of pathophysiological conditions responsible for disorders of the cardiovascular, immune, and central nervous systems. The recently solved cryo‐EM structure of TRPC3 provides detailed inputs about the underlying mechanistic aspects of the channel, which in turn enables more efficient ways of designing small‐molecule modulators. Pharmacologically targeting TRPC3 in animal models has demonstrated great efficacy in treating diseases including cancers, neurological disorders, and cardiovascular diseases. Despite extensive scientific evidence supporting some strong correlations between the expression and activity of TRPC3 and various pathophysiological conditions, therapeutic strategies based on its pharmacological modulations have not led to clinical trials. The development of small‐molecule TRPC3 modulators with high safety, sufficient brain penetration, and acceptable drug‐like profiles remains in progress. Determining the pathological mechanisms for TRPC3 involvement in human diseases and understanding the requirements for a drug‐like TRPC3 modulator will be valuable in advancing small‐molecule therapeutics to future clinical trials. In this review, we provide an overview of the origin and activation mechanism of TRPC3 channels, diseases associated with irregularities in their expression, and new development in small‐molecule modulators as potential therapeutic interventions for treating TRPC3 channelopathies.

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TRPC channels as emerging targets for seizure disorders

Cited by 9 publications

References 88 publications

Disposable Sensor Chips with Molecularly Imprinted Carbon Paste Electrodes for Monitoring Anti-Epileptic Drugs

Disposable Sensor Chips with Molecularly Imprinted Carbon Paste Electrodes for Monitoring Anti-Epileptic Drugs

Editorial: Neuroinflammation in acquired epilepsy

Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel

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