title: Altered NR4A Subfamily Gene Expression Level in Peripheral Blood of Parkinson's and Alzheimer's Disease Patients.
abstract: Parkinson's disease (PD) is a neurodegenerative pathology characterized by the degeneration of midbrain dopamine neurons, whose development and maintenance in brain is related to the transcription factor NR4A2 (also called Nurr1). Notably, NR4A2 is a neuroprotective agent with anti-inflammatory role in microglia and astrocytes. Furthermore, mutations in NR4A2 gene are associated to the familial form of PD, and its gene expression level is down-regulated in blood obtained from PD patients. NR4A2 belongs to the NR4A subfamily consisting of three members: NR4A1, NR4A2, and NR4A3. The NR4A subfamily shares high degree of homology in their molecular structure and cooperates in a spectrum of functions ranging from central nervous system to immune control during physiological and pathological conditions. Considering the close functional link between the member of NR4A subfamily, we performed a gene expression analysis of NR4A1, NR4A2, and NR4A3 in peripheral blood obtained from PD patients and healthy controls (HC). Then, in order to evaluate possible involvement of the NR4A subfamily in other neurodegenerative processes, we carried out the same analysis on blood obtained from Alzheimer's disease (AD) patients. A correlation between clinical features and gene expression was also evaluated. We found a marked down-regulated gene expression of the NR4A subfamily obtained from PD patients, but only a NR4A1 decrease in AD patients compared to HC. This study reports that the entire NR4A subfamily and not only NR4A2 could be systemically involved in PD suggesting that the study of these factors could be a promising approach to develop PD therapy.
authors.affiliation: Neurobiology Unit, Neurologia 2 - CReSM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin & AOU San Luigi Gonzaga, Regione Gonzole, 10, 10043, Orbassano, TO, Italy. francesca.montarolo@unito.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Montarolo
authors.affiliation: Neurobiology Unit, Neurologia 2 - CReSM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin & AOU San Luigi Gonzaga, Regione Gonzole, 10, 10043, Orbassano, TO, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Perga
authors.affiliation: Neurobiology Unit, Neurologia 2 - CReSM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin & AOU San Luigi Gonzaga, Regione Gonzole, 10, 10043, Orbassano, TO, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Martire
authors.affiliation: Neurobiology Unit, Neurologia 2 - CReSM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin & AOU San Luigi Gonzaga, Regione Gonzole, 10, 10043, Orbassano, TO, Italy.
authors.forename: Désirée Nicole
authors.initials: DN
authors.lastname: Navone
authors.affiliation: Division of Neurology, Martini Hospital, Via Tofane, 71, 10141, Turin, TO, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Marchet
authors.affiliation: Division of Neurology, Martini Hospital, Via Tofane, 71, 10141, Turin, TO, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Leotta
authors.affiliation: Neurobiology Unit, Neurologia 2 - CReSM (Regional Referring Center of Multiple Sclerosis), Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin & AOU San Luigi Gonzaga, Regione Gonzole, 10, 10043, Orbassano, TO, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D004268:DNA-Binding Proteins / Q000097:blood*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000097:blood*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000097:blood*; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy; D011987:Receptors, Steroid / Q000097:blood*; D011988:Receptors, Thyroid Hormone / Q000097:blood*
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539882:NR4A2 protein, human; C490412:NR4A3 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone
keywords: Alzheimer’s disease; NR4A subfamily; Neurodegenerative diseases; Nurr1; Parkinson’s disease