Targeted miRNA Delivery in Epilepsy: Mechanisms, Advances, and Therapeutic Potential

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: April 7, 2025

Language: Английский

Improving epilepsy management by targeting P2 × 7 receptor with ROS/electric responsive nanomicelles

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: May 5, 2025

The intricate pathogenesis of epilepsy, characterized by abnormal neuronal discharges and neuroinflammation, underscores the critical involvement adenosine triphosphate (ATP)-P2X purinoceptor 7 (P2 × 7) receptor pathway in inflammation activation. To address this, a reactive oxygen species (ROS)/electric-responsive d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-ferrocene-poloxamer nanomicelle (TFP@A) was engineered to deliver P2 antagonist A 438,079, aiming provide targeted therapeutic strategy for epilepsy management. study meticulously designed TFP@A precise drug delivery through various techniques including transmission electron microscopy (TEM), dynamic light scattering (DLS), high-performance liquid chromatography (HPLC). Cellular uptake blood-brain barrier (BBB) permeability were evaluated using fluorescein isothiocyanate (FITC)-labeled vitro brain endothelial cell line (bEnd.3) BBB model. In vivo distribution safety assessments conducted an mouse impact on investigated seizure analysis, electroencephalogram (EEG) recordings, inflammatory assessment. exhibited robust release profile under ROS electrical stimulation conditions. studies demonstrated its efficacy scavenging ROS, reducing oxidative stress, alleviating apoptosis models. Efficient cellular uptake, penetration, accumulation observed. Notably, effectively modulated 7R)-nucleotide-binding oligomerization domain-like family pyrin domain-containing 3 (NLRP3) pathway, inhibiting mediators promoting anti-inflammatory responses. loaded with showcases potential benefits suppressing NLRP3 inflammasome activation, mitigating microglial-neuron crosstalk, ameliorating symptoms, positioning it as promising avenue treatment.

Language: Английский

The role of miRNA134 in pathogenesis and treatment of intractable epilepsy: a review article

Nucleosides Nucleotides & Nucleic Acids, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 16

Published: March 26, 2024

MicroRNA-134 (miRNA134) has emerged as a critical regulator in the pathogenesis of epilepsy, particularly intractable cases resistant to conventional therapies. This review explores multifaceted roles miRNA134 epileptogenesis, focusing on its influence dendritic spine morphology and synaptic plasticity. Through interactions with proteins such LIM kinase 1 (LIMK1), Pumilio 2 (PUM2), Tubby-like protein (TULP1), modulates various molecular pathways implicated epilepsy development. Preclinical studies have shown pro­mising results targeting for mitigating seizure activity, highlighting potential therapeutic target. Furthermore, holds promise biomarker diagnosis prognosis, offering opportunities personalized treatment approaches. However, further research is warranted elucidate precise mechanisms underlying miRNA134's effects translate these findings into clinical applications.

Language: Английский