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

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Abstract

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.

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Acknowledgments

We would like to thank Egidio Caricati and Daniele Dell’Anna for their contribution to the compilation of database with healthy donors’ information and patients’ clinical data and Ishira Nanavaty for her relevant linguistic assistance.

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Author notes

  1. Serena Martire and Francesca Montarolo contributed equally to this work.

Authors and Affiliations

  1. Neurobiology Unit, Neurologia 2 – CReSM (Regional Referring Center Multiple Sclerosis), San Luigi Gonzaga University Hospital & Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano (TO), Italy

    Simona Perga, Serena Martire, Francesca Montarolo, Nicole D. Navone & Antonio Bertolotto

  2. 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

    Simona Perga

  3. “Rita Levi Montalcini” Department of Neuroscience, ALS (Amyotrophic Lateral Sclerosis) Expert Center (CRESLA), University of Turin & Città della Scienza e della Salute University Hospital, Turin, TO, Italy

    Andrea Calvo, Giuseppe Fuda & Adriano Chiò

  4. Division of Neurology, Martini Hospital, Turin, TO, Italy

    Alberto Marchet & Daniela Leotta

Authors
  1. Simona Perga
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  2. Serena Martire
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  3. Francesca Montarolo
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  4. Nicole D. Navone
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  5. Andrea Calvo
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  6. Giuseppe Fuda
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  7. Alberto Marchet
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  8. Daniela Leotta
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  9. Adriano Chiò
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  10. Antonio Bertolotto
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Corresponding author

Correspondence to Simona Perga.

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Funding

The study was supported by the Italian Ministry of Health (Bando Giovani Ricercatori 2010—Grant number GR-2010-2315964), the Fondazione Italiana Sclerosi Multipla (FISM—Grant number 2010/R/7), and the European Community’s Health Seventh Framework Programme (FP7/2007–2013 under grant agreement 259867).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Perga, S., Martire, S., Montarolo, F. et al. A20 in Multiple Sclerosis and Parkinson’s Disease: Clue to a Common Dysregulation of Anti-Inflammatory Pathways?. Neurotox Res 32, 1–7 (2017). https://doi.org/10.1007/s12640-017-9724-y

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  • DOI: https://doi.org/10.1007/s12640-017-9724-y

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