The effect of valproic acid and furosemide on the regulation of the inflammasome complex (NLRP1 and NLRP3 mRNA) in the brain of epileptic animal model

Samadianzakaria, Aref; Abdolmaleki, Zohreh; Faedmaleki, Firouz

doi:10.1016/j.brainresbull.2022.10.002

“…2024, 25, x FOR PEER REVIEW 6 of 25 epilepsy in rats [88]. Recently, the expression of NLRP1 and NLRP3 mRNAs was significantly increased in the animal model of epilepsy induced by the intrahippocampal injection of KA compared to controls [89].…”

Section: Current Antiseizure Medications For the Treatment Of Epilepsymentioning

confidence: 99%

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

Haque,

Thapa,

Burns

et al. 2024

IJMS

0

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Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.

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“…Gao et al reported an elevated expression of the NLRP1 6 inflammasome in hippocampi from the pentylenetetrazol (PTZ) kindling model of epilepsy in rats [88]. Recently, the expression of NLRP1 and NLRP3 mRNAs was significantly increased in the animal model of epilepsy induced by the intrahippocampal injection of KA compared to controls [89].…”

Section: Nlrp3 Inflammasome Involvement In Epilepsymentioning

confidence: 99%

“…Recent research suggest that increased activity of NLRP3 contributes to the development and progression of epilepsy [68,70,71,[73][74][75]117]; hence, inhibiting the activity of NLRP3 may reduce inflammation-caused epileptic injuries and potentially improve symptoms [89]. NLRP3 inhibitors, a potential new class of drugs, might have fewer side effects and be more effective in a larger number of patients, and could target the underlying causes of epilepsy.…”

Section: Nlrp3 Inflammasome In Epilepsymentioning

confidence: 99%

“…Huperzine A, a naturally occurring sesquiterpene alkaloid and valproic acid, and one of the most prescribed medications against epilepsy, has been shown to inhibit activation of the NLRP3 inflammasome in the rat KA-induced model of epilepsy in a ROS-dependent manner [172]. Recently, furosemide (4-chloro-5-sulphonyl-N-furfuryl-anthranilic acid), a diuretic drug, has been shown to decrease the NLRP3 as well as NLRP1 level significantly when treated in with valproic acid in KA-induced epileptic rats [89].…”

Section: Cy-09 (4-[[4-oxo-2-thioxo-3-[[3-(trifluoromethyl) Phenyl] Me...mentioning

confidence: 99%

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NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

Haque,

Thapa,

Burns

et al. 2024

Preprint

0

View full text Add to dashboard Cite

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

show abstract

“…Gao et al reported an elevated expression of the NLRP1 inflammasome in hippocampi from the pentylenetetrazol (PTZ) kindling model of epilepsy in rats [88]. Recently, the expression of NLRP1 and NLRP3 mRNAs were significantly increased in the animal model of epilepsy induced by intrahippocampal injection of KA compared to controls [89].…”

Section: Nlrp3 Inflammasome Involvement In Epilepsymentioning

confidence: 99%

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

Haque,

Thapa,

Burns

et al. 2024

Preprint

0

View full text Add to dashboard Cite

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

show abstract

The effect of valproic acid and furosemide on the regulation of the inflammasome complex (NLRP1 and NLRP3 mRNA) in the brain of epileptic animal model

Cited by 12 publications

References 60 publications

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development

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