癫痫是一种中枢神经系统(CNS)疾病,由于大脑电活动的短暂过度或同步改变而导致反复发作。几种神经系统疾病与麸质相关疾病(GRD)有关,包括癫痫。然而,GRD与癫痫发生相关的分子机制尚不清楚.我们先前的数据表明,麦醇溶蛋白肽31-43(p31-43)增加了小鼠中红藻氨酸诱导的癫痫发作的数量和持续时间,并加剧了器官型海马切片中CA3-红藻氨酸诱导的神经毒性。这里,我们研究了另一种重要的麦醇溶蛋白肽p57-68是否可能对海藻酸盐诱导的神经毒性产生与p31-43相似的作用.我们发现,一旦同时受到攻击,两种肽都会加剧海藻酸盐诱导的CA3区域损伤。然而,预孵育后,p31-43还加剧了CA1区的神经毒性,而P57-68没有。这些数据表明由肽激活的差异细胞内机制。的确,分析细胞内信号通路,我们发现p31-43诱导显著的细胞内变化,包括Akt的磷酸化增加,Erk1/2和p65,减少p38磷酸化,和核组蛋白-3的脱乙酰化。基于这些观察,我们证明p31-43可能激活参与神经元兴奋性的特定细胞内信号通路,炎症,和表观遗传调控,这可能有助于其进一步加重红藻氨酸盐诱导的神经毒性。相比之下,p57-68似乎通过不同的机制发挥其作用。需要进一步的研究来阐明这些肽影响神经毒性的确切机制,并了解它们对神经系统疾病的影响。
Epilepsy is a central nervous system (CNS) disorder causing repeated seizures due to a transient excessive or synchronous alteration in the electrical activity of the brain. Several neurological disorders have been associated to gluten-related diseases (GRD), including epilepsy. However, the molecular mechanisms that associate GRD and epileptogenesis are still unknown. Our previous data have shown that the gliadin peptide 31-43 (p31-43) enhanced number and duration of seizures induced by kainate in mice and exacerbated CA3-kainate-induced
neurotoxicity in organotypic hippocampal slices. Here, we investigated whether another important gliadin peptide p57-68 may exerts effects similar to p31-43 on kainate-induced
neurotoxicity. We find that both peptides exacerbate kainate-induced damage in the CA3 region once simultaneously challenged. However, after pre-incubation, p31-43 additionally exacerbates
neurotoxicity in the CA1 region, while p57-68 does not. These data suggested differential intracellular mechanisms activated by the peptides. Indeed, analysing intracellular signalling pathways we discover that p31-43 induces significant intracellular changes, including increased phosphorylation of Akt, Erk1/2, and p65, decreased p38 phosphorylation, and deacetylation of nuclear histone-3. Based on these observations, we demonstrate that p31-43 likely activates specific intracellular signaling pathways involved in neuronal excitability, inflammation, and epigenetic regulation, which may contribute to its exacerbation of kainate-induced
neurotoxicity. In contrast, p57-68 appears to exert its effects through different mechanisms. Further research is necessary to elucidate the precise mechanisms by which these peptides influence
neurotoxicity and understand their implications for neurological disorders.