The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice
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 coul...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2020-05-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/13/5/dmm043513 |
| _version_ | 1811323179940970496 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Valeria Valsecchi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T13:50:31Z |
| format | Article |
| id | doaj.art-e0628cfe21604ba9afc32b7db641016e |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-04-13T13:50:31Z |
| publishDate | 2020-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-e0628cfe21604ba9afc32b7db641016e2022-12-22T02:44:22ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-05-0113510.1242/dmm.043513043513The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A miceValeria Valsecchi0Marina Boido1Francesca Montarolo2Michela Guglielmotto3Simona Perga4Serena Martire5Santina Cutrupi6Andrea Iannello7Nadia Gionchiglia8Elena Signorino9Andrea Calvo10Giuseppe Fuda11Adriano Chiò12Antonio Bertolotto13Alessandro Vercelli14 Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10126 Turin, Italy Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10126 Turin, Italy Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, Turin, Italy Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10126 Turin, Italy Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10126 Turin, Italy Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, Turin, Italy Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Turin, Italy Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Turin, Italy Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, Turin, Italy Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, Turin, Italy Department of Neuroscience Rita Levi Montalcini, Amyotrophic Lateral Sclerosis Expert Center (CRESLA), University of Turin, via Cherasco 15, 10126 Turin, Italy Department of Neuroscience Rita Levi Montalcini, Amyotrophic Lateral Sclerosis Expert Center (CRESLA), University of Turin, via Cherasco 15, 10126 Turin, Italy Department of Neuroscience Rita Levi Montalcini, Amyotrophic Lateral Sclerosis Expert Center (CRESLA), University of Turin, via Cherasco 15, 10126 Turin, Italy Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, Turin, Italy Department of Neuroscience Rita Levi Montalcini, University of Turin, via Cherasco 15, 10126 Turin, Italy 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.http://dmm.biologists.org/content/13/5/dmm043513alssod1-g93a micemotor neuron diseaseneuroinflammationnurr1 |
| spellingShingle | 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 The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice Disease Models & Mechanisms als sod1-g93a mice motor neuron disease neuroinflammation nurr1 |
| title | The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice |
| title_full | The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice |
| title_fullStr | The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice |
| title_full_unstemmed | The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice |
| title_short | The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice |
| title_sort | transcription factor nurr1 is upregulated in amyotrophic lateral sclerosis patients and sod1 g93a mice |
| topic | als sod1-g93a mice motor neuron disease neuroinflammation nurr1 |
| url | http://dmm.biologists.org/content/13/5/dmm043513 |
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