The transcription factor Nurr1 is up-regulated in Amyotrophic Lateral Sclerosis patients and SOD1-G93A mice

Disease Models and Mechanisms , 18 Match 2020
The transcription factor Nurr1 is up-regulated in Amyotrophic Lateral Sclerosis patients and SOD1-G93A mice

Valeria Valsecchi ^{1 2 3 *} , Marina Boido ^{4 2 *} , Francesca Montarolo ^{2 5} , Michela Guglielmotto ^{4 2} , Simona Perga ^{4 2 5} , Serena Martire ^{2 5} , Santina Cutrupi ⁶ , Andrea Iannello ⁶ , Nadia Gionchiglia ² , Elena Signorino ² , Andrea Calvo ^{7 8} , Giuseppe Fuda ^{7  8} , Adriano Chiò ^{7 8} , Antonio Bertolotto ^{2 5} , Alessandro Vercelli ^{4 2}

* these authors eqaully contributed to the article

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons (MNs) in the central nervous system (CNS). ALS etiology is highly multifactorial and multifarious, and an effective treatment is still lacking. Neuroinflammation is a hallmark of ALS and could be targeted to develop new therapeutic approaches. Interestingly, the transcription factor Nurr1 has been demonstrated to play an important role in inflammatory process in several neurological disorders, such as Parkinson’s disease (PD) and Multiple Sclerosis (MS).

In the present paper, we demonstrated for the first time that Nurr1 expression levels were up-regulated in the peripheral blood of ALS patients. Moreover, we investigated Nurr1 function in the SOD1-G93A mouse model of ALS. Interestingly, Nurr1 was strongly up-regulated in the spinal cord during the asymptomatic and early symptomatic phases of the disease, where it promoted the up-regulation of the BDNF mRNA and the repression of NF-kB pro-inflammatory targets, such as iNOS. Therefore, we hypothesize that Nurr1 is activated in an early phase of the disease as survival endogenous mechanism, although not sufficient to revert disease progression.

¹  Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10126, Turin, Italy valsecchiv@yahoo.com .
²  Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043, Orbassano, Turin, Italy.
³  Department of Neuroscience, Reproductive and Dentistry Sciences, University of Naples "Federico II", via S.Pansini 5, 80131, Naples, Italy.
⁴  Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10126, Turin, Italy.
⁵  Neurobiology Unit, Neurology - CReSM (Regional Referring Center of Multiple Sclerosis), AOU San Luigi Gonzaga, Regione Gonzole 10, 10043, Orbassano, Turin, Italy.
⁶  Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043, Orbassano (TO), Italy.
⁷  Department of Neuroscience Rita Levi Montalcini, Amyotrophic Lateral Sclerosis Expert Center (CRESLA), University of Turin, via Cherasco 15, 10126, Turin, Italy.
⁸  University Hospital Città della Scienza e della Salute, corso Bramante 88, 10126, Turin, Italy.