A20 in Multiple Sclerosis and Parkinson’s Disease: Clue to a Common Dysregulation of Anti-Inflammatory Pathways?

• Published in: Neurotoxicity research Vol. 32; no. 1; pp. 1 - 7
• Main Authors: Perga, Simona, Martire, Serena, Montarolo, Francesca, Navone, Nicole D., Calvo, Andrea, Fuda, Giuseppe, Marchet, Alberto, Leotta, Daniela, Chiò, Adriano, Bertolotto, Antonio
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-07-2017
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Alzheimer Disease - blood; Amyotrophic Lateral Sclerosis - blood; Biomedical and Life Sciences; Biomedicine; Cell Biology; Female; Gene Expression; Humans; Italy; Male; Middle Aged; Multiple Sclerosis - blood; Neurobiology; Neurochemistry; Neurology; Neurosciences; Parkinson Disease - blood; Pharmacology/Toxicology; RNA, Messenger - metabolism; Short Communication; Tumor Necrosis Factor alpha-Induced Protein 3 - blood; Tumor Necrosis Factor alpha-Induced Protein 3 - genetics; Parkinson diseases; Multiple sclerosis; A20/TNFAIP3; Systemic chronic inflammation; NF-kB; Amyotrophic lateral sclerosis; Alzheimer’s diseases
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-017-9724-y

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.