Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.
Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.
Neurosci Lett. 2021 Jan 1;740:135487. doi: 10.1016/j.neulet.2020.135487. Epub 2020 Nov 5.
Parkinson's disease (PD) is a complex neurodegenerative disorder, resulting dopaminergic neuronal cell death in the substantia nigra. The disease is characterized by major motor impairment, being bradykinesia, rest tremor, rigidity and loss of postural reflexes the most common, while autonomic dysfunctions, sleep disturbances and psychiatric disorders are some of the wide range of non-motor symptoms. Several processes have been identified to be associated with disease development, such as mitochondrial dysfunction, oxidative/nitrosative stress and neuroinflammation. NF-κB is an important transcription factor that regulates several inflammatory elements and pathways, and polymorphisms on NFKB1 and NFKBIA genes can potentially influence redox balance towards a pro-oxidative frame, modulating disease progression. Evaluation of these polymorphisms in the redox status of PD subjects could provide new insights on the pathogenesis of this disorder. The study aimed to test associations of -94 in./del ATTG NFKB1 (rs28362491) and c.*126G > A NFKBIA (rs696) polymorphisms with PD development, and to test the influence of both polymorphisms on oxidative/nitrosative stress (OS/NS) parameters. A total of 110 Brazilian individuals were enrolled, being 55 subjects recruited from University Hospital of Londrina as the PD group, and 55 subjects matched for age, sex and ethnicity composed the healthy control (HC) group. NFkB1 and NFkBIA polymorphisms were genotyped by PCR-RFLP. Lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), sulfhydryl groups (SH), total radical trapping antioxidant parameter (TRAP) and paraoxonase-1 activity (PON-1) were assessed. Despite no association of polymorphisms on disease development was observed, in PD subjects the NFKB1 del/del genotype was associated with higher levels of LOOH, while NFkBIA GA and AA genotypes were associated with higher NOx levels, suggesting that NFkB plays a role in PD susceptbility. In conclusion, the prospect of genetic polymorphisms of elements involved in inflammation and OS/NS might be a new approach to unravel PD etiology.
帕金森病（PD）是一种复杂的神经退行性疾病，导致黑质中多巴胺能神经元死亡。该疾病的特征是主要运动障碍，运动迟缓、静止性震颤、僵硬和姿势反射丧失最为常见，而自主功能障碍、睡眠障碍和精神障碍则是广泛的非运动症状之一。已经确定了几个与疾病发展相关的过程，例如线粒体功能障碍、氧化/硝化应激和神经炎症。NF-κB 是一种重要的转录因子，可调节多种炎症成分和途径，NFKB1 和 NFKBIA 基因的多态性可能会影响氧化还原平衡，使其向促氧化状态转变，从而调节疾病的进展。评估 PD 患者的这些多态性与氧化还原状态之间的关系，可以为该疾病的发病机制提供新的见解。本研究旨在检验-94 in./del ATTG NFKB1（rs28362491）和 c.*126G > A NFKBIA（rs696）多态性与 PD 发病之间的关系，并检验这两种多态性对氧化/硝化应激（OS/NS）参数的影响。共纳入了 110 名巴西人，其中 55 名受试者来自朗德里纳大学医院，被招募为 PD 组，55 名年龄、性别和种族相匹配的受试者组成健康对照组（HC）。通过 PCR-RFLP 对 NFkB1 和 NFkBIA 多态性进行基因分型。评估脂质氢过氧化物（LOOH）、一氧化氮代谢物（NOx）、高级氧化蛋白产物（AOPP）、巯基（SH）、总自由基捕获抗氧化参数（TRAP）和对氧磷酶-1 活性（PON-1）。尽管多态性与疾病发展无关，但在 PD 患者中，NFKB1 del/del 基因型与 LOOH 水平升高相关，而 NFKBIA GA 和 AA 基因型与 NOx 水平升高相关，表明 NFkB 在 PD 易感性中起作用。总之，涉及炎症和 OS/NS 的元素的遗传多态性可能是揭示 PD 病因的新方法。
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