The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice

• Main Authors: Valeria Valsecchi, Marina Boido, Francesca Montarolo, Michela Guglielmotto, Simona Perga, Serena Martire, Santina Cutrupi, Andrea Iannello, Nadia Gionchiglia, Elena Signorino, Andrea Calvo, Giuseppe Fuda, Adriano Chiò, Antonio Bertolotto, Alessandro Vercelli
• Format: Article
• Language: English
• Published: The Company of Biologists 2020-05-01
• Series: Disease Models & Mechanisms
• Subjects: als; sod1-g93a mice; motor neuron disease; neuroinflammation; nurr1
• Online Access: http://dmm.biologists.org/content/13/5/dmm043513
• ISSN: 1754-8403; 1754-8411

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons (MNs) in the central nervous system. 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 have an important role in the inflammatory process in several neurological disorders, such as Parkinson's disease and multiple sclerosis. In the present paper, we demonstrate for the first time that Nurr1 expression levels are upregulated in the peripheral blood of ALS patients. Moreover, we investigated Nurr1 function in the SOD1-G93A mouse model of ALS. Nurr1 was strongly upregulated in the spinal cord during the asymptomatic and early symptomatic phases of the disease, where it promoted the expression of brain-derived neurotrophic factor mRNA and the repression of NFκB pro-inflammatory targets, such as inducible nitric oxide synthase. Therefore, we hypothesize that Nurr1 is activated in an early phase of the disease as a protective endogenous anti-inflammatory mechanism, although not sufficient to reverse disease progression. On the basis of these observations, Nurr1 could represent a potential biomarker for ALS and a promising target for future therapies.