Neurochemical Research, Год журнала: 2024, Номер 50(1)
Опубликована: Дек. 7, 2024
Язык: Английский
Pharmacological Reports, Год журнала: 2025, Номер unknown
Опубликована: Янв. 27, 2025
Язык: Английский
Процитировано
2
Current Treatment Options in Neurology, Год журнала: 2025, Номер 27(1)
Опубликована: Янв. 24, 2025
Язык: Английский
Процитировано
0
Chinese Medical Journal, Год журнала: 2025, Номер unknown
Опубликована: Март 11, 2025
Abstract Background: The CUG-binding protein Elav-like family member 2 ( CELF2 ) gene has been linked to the pathogenesis of epilepsy, but its precise role remains unclear. This study aimed investigate pathogenic mechanisms mutation in utilizing zebrafish models explore molecular pathways and biological impact. Methods: Whole-exome sequencing was performed identify mutations associated with epilepsy. model were generated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-related 9 technology morpholinos, followed by behavioral electroencephalographic analyses confirm epileptic phenotypes. Proteomic metabolomic conducted examine impact deficiency on metabolic pathways, single-cell used assess alterations neuronal cell populations. Results: An infant infantile spasms syndrome a p.Pro520Arg reported. We established celf2 knockout knockdown found that exhibited epilepsy-like behaviors, which could be rescued injection wild-type mRNA. Significant changes observed crucial marker genes nervous system +/− group, including FOS , BDNF NPAS4 GABRA1 GABRG2 PYYA . Disruptions lipid metabolism, heat shock 90 beta1 (Hsp90b1), identified proteomic analyses. Single-cell showed nucleosome localization, DNA binding, arginine proline gonadotropin-releasing hormone signaling pathway, nucleotide-binding oligomerization domain receptor pathway. Conclusions: Our revealed promising association between defects epilepsy model, suggesting CLEF2 is causative These findings not only indicate potential process influenced defect also offer hopeful insights into therapeutic targets.
Язык: Английский
Процитировано
0
Cellular and Molecular Immunology, Год журнала: 2025, Номер unknown
Опубликована: Март 13, 2025
Abstract Neuroinflammation plays an important role in the pathogenesis of various central nervous system (CNS) diseases. The NLRP3 inflammasome is intracellular multiprotein complex composed innate immune receptor NLRP3, adaptor protein ASC, and protease caspase-1. activation can induce pyroptosis release proinflammatory cytokines IL-1β IL-18, thus playing a inflammatory responses. Recent studies have revealed that activated brain to neuroinflammation, leading further neuronal damage functional impairment, contributes pathological process neurological diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s stroke. In this review, we summarize neuroinflammation course CNS diseases discuss potential approaches target for treatment
Язык: Английский
Процитировано
0
Frontiers in Neuroscience, Год журнала: 2025, Номер 19
Опубликована: Март 27, 2025
Epilepsy is the second most common neurological disorder and affects approximately 50 million people worldwide. Despite advances in antiepileptic therapy, about 30% of patients develop refractory epilepsy. Recent studies have shown sleep, glymphatic function, cerebral small vessel disease (CSVD), epilepsy are interrelated by sharing a multidirectional relationship influencing their severity progression. Sleep plays vital role brain homeostasis promotes clearance responsible for removal metabolic wastes neurotoxic substances from brain. Disrupted sleep feature can lead to impairment efficiency or glymphopathy, promoting neuroinflammation accrual epileptogenic factors. CSVD, occurring up 60% aging population, further exacerbates neurovascular compromise neurodegeneration increasing seizure susceptibility worsening outcomes. This narrative review aims discuss molecular pathophysiological inter-relationships between these factors, providing new framework that places glymphopathy CSVD as contributors epileptogenesis conditions disruption. We propose an integrative model wherein vascular insufficiency interact positive feedback loop disruption increased vulnerability mediated epileptic activity. Acknowledging interactions has significant impacts on both research clinical practice. Targeting modulation, cerebrovascular health presents promising avenue therapeutic intervention. Future should focus developing precision medicine approaches integrate neuro-glial-vascular mechanisms optimize management. Clinically, addressing disturbances may improve treatment effectiveness, reduce burden, overall highlights need interdisciplinary break vicious cycle epilepsy, disturbance, pathology, paving way innovative paradigms.
Язык: Английский
Процитировано
0
Heliyon, Год журнала: 2024, Номер 10(19), С. e38050 - e38050
Опубликована: Сен. 19, 2024
Язык: Английский
Процитировано
0
Chemistry & Biodiversity, Год журнала: 2024, Номер unknown
Опубликована: Окт. 11, 2024
Abstract 1. The toxicity of derivatives was removed by the reasonable modification bioactive skeleton. 2. As potential COX‐2 inhibitor with IC 50 values ranging from 39.42 to 179.84 nM/L, compounds ( Q4‐Q10 , Q20 ) exhibited superior anti‐inflammatory activity at low micromolar concentrations. 3. Q7 (IC (COX‐2)= 61.05 nM/L), Q10 54.68 nM/L) and showed stronger inhibitory abilities than Celecoxib 67.89 nM/L). 4. strongest agent, NO = 9.96 μM/L, effectively inhibited secretion IL‐1β TNF‐α, 12.30 9.07 μM/L respectively. 5. exerted as actives via targeting COX‐2, down‐regulating iNOS TLR4 protein, inhibiting activation NLRP3 inflammasome NF‐κB signal pathway.
Язык: Английский
Процитировано
0
Neurochemical Research, Год журнала: 2024, Номер 50(1)
Опубликована: Дек. 7, 2024
Язык: Английский
Процитировано
0