The Emerging Role of Toll-Like Receptor-Mediated Neuroinflammatory Signals in Psychiatric Disorders and Acquired Epilepsy

Chaudhary, Anubha; Mehra, Parul; Keshri, Anand K; Rawat, Suraj S; Mishra, Amit; Prasad, Amit

doi:10.1007/s12035-023-03639-7

Cited by 1 publication

(2 citation statements)

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“…TLR signaling emerges as a pivotal factor in epilepsy pathogenesis, evident from brain inflammation observed in both clinical cases and experimental models [185][186][187]271,272]. Of particular significance is the interaction between HMGB1 and TLR4 in this pathway, which plays a pivotal role in seizure generation and perpetuation.…”

Section: Toll-like Receptor Signaling and Neuroimmune Regulationmentioning

confidence: 99%

“…Advancements in understanding the molecular intricacies of the innate immune system, particularly TLR signaling, have unveiled its significant contribution to seizure activity. Activation of TLR signaling results in increased production of various inflammatory modulators [187,271,272,[444][445][446][447], along with rapid post-translational changes in ion channels that enhance excitability and transcriptional alterations in genes associated with neurotransmission and synaptic plasticity, ultimately reducing seizure thresholds chronically [186,448]. Experimental studies have demonstrated the critical role of TLR4 in seizure initiation and propagation, with its ligand HMGB1 emerging as a potential therapeutic target [440,449].…”

Section: Seizure Disordersmentioning

confidence: 99%

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Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders

Balan,

Boero,

Chéry

et al. 2024

Life

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Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors. Androstane neuroactive steroids, including estrogens and androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression and activation. Notably, androstenediol (ADIOL), an androstane neurosteroid, emerges as a potent anti-inflammatory agent, promising for therapeutic interventions. The dysregulation of immune responses via TLR signaling alongside reduced levels of endogenous neurosteroids significantly contributes to symptom severity across various neuropsychiatric disorders. Neuroactive steroids, such as allopregnanolone, demonstrate efficacy in alleviating symptoms of various neuropsychiatric disorders and modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research aimed at unraveling the intricacies of neuropsychiatric disorders.

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