NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-β in sclerotic hippocampi

Targeting Inflammasomes to Treat Neurological Diseases

“…Increased expression of NLRP1 and active caspase‐1 was found in surgically resected hippocampus of patients with mesial TLE, and double immunofluorescent staining revealed the neuronal source of NLRP1 expression in these patients 56 . In a recent study, an increased expression of both NLRP1 and NLRP3 inflammasomes was observed in the sclerotic hippocampi of patients with mesial TLE 57 . In a rat model of TLE, NLRP1 deficiency was associated with reduced neuronal pyroptosis and decreased frequency and severity of seizures 56 .…”

Semaglutide attenuates seizure severity and ameliorates cognitive dysfunction by blocking the NLR family pyrin domain containing 3 inflammasome in pentylenetetrazole‑kindled mice

“…Activation of the NLRP3 inflammasome induces the secretion of IL-1β and IL-18 (38), and IL-1β further induces the release of IL-6 and TNF-α (43). Both inflammasomes and neuroinflammation affect the occurrence and development of epilepsy, and anti-inflammasome and anti-neuroinflammation therapies may be novel treatments for epilepsy (16). In the present study, semaglutide attenuated NLRP3 inflammasome activation and inflammatory cytokine secretion in LPS-and nigericin-induced inflammatory BV2 cells.…”

“…The NLRP3 inflammasome results from the assembly of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and caspase-1 (14), and promotes the secretion of inflammatory cytokines, influencing the pathophysiology of epilepsy (14). Additionally, in animal and clinical epilepsy-related research, increased levels of the NLRP3 inflammasome and neuroinflammatory cytokines have been detected in hippocampal tissues (15,16), suggesting their close association with epileptogenesis. Moreover, numerous studies have reported that inhibiting NLRP3 activation and inflammatory cytokine secretion decreases to occurrence of epileptic seizures and ameliorates cognitive dysfunction (17,18).…”

β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice

“…NLRP3 are upregulated and expressed by both glial and neuronal cells in sclerotic hippocampi from patients with temporal lobe epilepsy. NLRP3 inflammasome signaling triggers the production of the proinflammatory mediators IL-1β and then releases proinflammatory cytokines TNF-α ( Cristina de Britotoscano et al, 2021 ). Activation of the NLRP3 inflammasome induces systemic chronic inflammation in aging.…”