[Expression Profiles of TRIM Family Genes in Neuronal and Glial Cell Cultures of Healthy Donors and Patients with Parkinson's Disease under Normal Conditions and Upon Neuroinflammation].

V V Nenasheva, E V Novosadova, T P Gerasimova, L V Novosadova, A Y Kotok, E L Arsenieva, E A Stepanenko, I A Grivennikov, V Z Tarantul
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Abstract

Proteins of the TRIM family are involved in both innate immunity and the nervous system processes and may play an important role in the development of neurodegenerative diseases. In this work, we analyzed the expression of 35 genes of the TRIM family in neural progenitors (NPs), terminally differentiated neurons (TDNs) and glial derivatives (NGs) obtained from induced pluripotent stem cells (iPSCs) of healthy donors (HD) and patients with Parkinson's disease (PD), in the absence of inflammatory stimuli and upon the induction of a nonspecific inflammatory response under the influence of TNFα. In NPs and TDNs of PD patients, compared with HD cells, differences in expression were observed for only a small number of TRIM genes. Under the influence of TNFα in TDNs, the expression of individual TRIM genes was activated, which was more significant in the cells of patients with PD compared to cells of HDs. In NGs of PD patients, the expression of many TRIM genes was initially reduced compared to HD cells and remained low or further decreased after exposure to TNFα. The data obtained demonstrate differences in the network of the TRIM family members in PD neurons and glia compared to control, and also show the multidirectional influence of the inflammatory stimulus on the expression of a number of TRIM genes in these types of cells. Considering the important role of many TRIM genes in the functioning of the innate immune system, it can be assumed that, in PD, more significant disturbances in the functioning of genes of this family occur in glia compared to neurons.

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[TRIM家族基因在健康供体和帕金森病患者神经元和胶质细胞培养物中正常状态和神经炎症时的表达谱]。
TRIM家族蛋白参与先天免疫和神经系统过程,并可能在神经退行性疾病的发展中发挥重要作用。在这项工作中,我们分析了TRIM家族35个基因在健康供体(HD)和帕金森病(PD)患者的诱导多能干细胞(iPSCs)中获得的神经祖细胞(NPs)、终末分化神经元(tdn)和胶质衍生物(ng)中的表达,在没有炎症刺激和TNFα影响下诱导非特异性炎症反应。在PD患者的NPs和tdn中,与HD细胞相比,只有少数TRIM基因的表达存在差异。在tdn中tnf - α的影响下,个体TRIM基因的表达被激活,PD患者细胞中比hd细胞更明显。在PD患者的NGs中,与HD细胞相比,许多TRIM基因的表达最初降低,并在暴露于TNFα后保持低水平或进一步降低。所获得的数据表明,与对照组相比,TRIM家族成员在PD神经元和胶质细胞中的网络存在差异,并显示炎症刺激对这些类型细胞中多个TRIM基因表达的多向影响。考虑到许多TRIM基因在先天免疫系统功能中的重要作用,可以假设,在PD中,与神经元相比,该家族基因功能的紊乱更明显地发生在胶质细胞中。
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来源期刊
Molekulyarnaya Biologiya
Molekulyarnaya Biologiya Medicine-Medicine (all)
CiteScore
0.70
自引率
0.00%
发文量
131
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