Perga Simona, Martire Serena, Montarolo Francesca, Navone Nicole D, Calvo Andrea, Fuda Giuseppe, Marchet Alberto, Leotta Daniela, Chiò Adriano, Bertolotto Antonio
Neurobiology Unit, Neurologia 2 - CReSM (Regional Referring Center Multiple Sclerosis), San Luigi Gonzaga University Hospital & Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano (TO), Italy.
Neurobiology Unit, Neurologia 2 - CRESM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO) University of Turin & AOU San Luigi, Regione Gonzole, 10, 10043, Orbassano, TO, Italy.
Neurotox Res. 2017 Jul;32(1):1-7. doi: 10.1007/s12640-017-9724-y. Epub 2017 Mar 23.
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.
慢性炎症在多种神经退行性疾病的发病机制中起着重要作用。在生理条件下，一旦引发损伤被消除，急性炎症反应终止，慢性炎症状态就会得到预防。多种机制调节炎症的消退。其中，一种名为A20的促炎NF-κB信号的强效抑制剂已成为关键因素。最近的研究表明，多种慢性炎症性疾病患者的血液中A20水平降低。在多发性硬化症（MS）患者中也得到了类似的结果，MS是一种以持续炎症为特征的神经退行性疾病。在本研究中，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）与健康对照（HC）和未接受治疗的MS患者相比，是否也表现出A20表达失调。我们的结果证实了先前的数据，即与HC相比，MS患者全血中的A20表达降低。此外，我们证明PD患者中A20表达也明显降低。A20通路的失调可能导致这些疾病中炎症的持续存在。因此，进一步研究不同炎症性疾病之间这种常见的失调通路是否可能代表新的治疗靶点将是很有趣的。
