A20 in Multiple Sclerosis and Parkinson's Disease: Clue to a Common Dysregulation of Anti-Inflammatory Pathways?
A20 in Multiple Sclerosis and Parkinson's Disease: Clue to a Common Dysregulation of Anti-Inflammatory Pathways?
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DOI：
10.1007/s12640-017-9724-y
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发表时间：
2017-07-01
影响因子：
3.7
通讯作者：
Bertolotto, Antonio
中科院分区：
文献类型：
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作者：
Perga, Simona;Martire, Serena;Bertolotto, Antonio
慢性炎症在几种神经退行性疾病的发病机制中起重要作用。在生理条件下，一旦消除了触发的侮辱，就通过终止急性炎症反应来防止慢性炎症状态。有几种机制调节炎症的消退。其中，一种被称为A20的促炎性核因子-kB信号的有效抑制剂已经成为关键参与者。最近的研究表明，在各种慢性炎症性疾病的患者中，A20的血液水平降低。类似的结果也被证明在多发性硬化症(MS)患者中，这是一种以持续性炎症为特征的神经退行性疾病。在目前的研究中，我们调查了其他类似的神经退行性疾病，如帕金森病(PD)、阿尔茨海默病(AD)和肌萎缩侧索硬化症(ALS)是否也显示出与健康对照组(HC)和未接受治疗的MS患者相比，A20表达水平降低。我们的结果证实了先前的数据，与HC相比，MS患者全血中A20的表达减少。此外，我们还证明A20的表达在帕金森病患者中也很明显。A20通路的失调可能会导致炎症在这些疾病中持续存在。因此，进一步研究不同炎症性疾病之间这些通常被解除管制的途径是否可以代表新的治疗靶点将是一件有趣的事情。
Chronic inflammation significantly contributes to the pathogenesis of several neurodegenerative disorders. In physiological conditions, a chronic inflammatory state is prevented through the termination of the acute inflammatory response once the triggering insult is eliminated. Several mechanisms regulate the resolution of inflammation. Among these, a potent inhibitor of the pro-inflammatory NF-kB signaling known as A20 has emerged as a key player. Recent studies have shown reduced blood levels of A20 in the patients of diverse chronic inflammatory diseases. Similar results have also been demonstrated in patients of multiple sclerosis (MS), a neurodegenerative disease characterized by persisting inflammation. In the present study, we investigate whether other similar neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) also demonstrate deregulated levels of A20 expression as compared to healthy controls (HC) and treatment-naive MS patients. Our results confirm previous data that the A20 expression is reduced in whole blood of MS patients as compared to HC. Additionally, we demonstrate that significantly diminished A20 expression is also evident in PD patients. The dysregulation of the A20 pathway could then contribute to the persistence of inflammation in these disorders. It would thus be interesting to investigate further whether such commonly deregulated pathways between different inflammatory diseases could represent novel targets for therapy.