There is a highly homologous NURR1 gene in humans (formerly known as NOT) which therefore constitutes a good candidate gene for neurologic and psychiatric disorders with an involvement of the dopamine neuron system, such as Parkinson's disease, schizophrenia, and manic-depression.
Altogether, the enhancement of tyrosine hydroxylase in naïve dopaminergic cells and the protective effects in a cellular model of Parkinson's disease suggest that full-length Nurr1 fusion protein may contribute to the development of a novel concept of protein-based therapy.
Our data indicate that Nurr1 plays an important role in the functional maintenance and survival of nigral DAergic neurons and suggest that the Nurr1+/- mouse is a useful animal model to study the pathogenesis of Parkinson disease (PD) and to explore disease-modifying strategies.
In parallel, NURR1 has been also linked to dopamine-associated brain disorders, such as Parkinson's disease (PD) and schizophrenia, since it is involved in the development and in the maintenance of midbrain dopaminergic neurons (mDA).
Nuclear receptor related 1 (NURR1) is an essential protein for maintenance of dopaminergic neurons in adult midbrain of which deficiency leads to Parkinson's disease.
These data highlight the role of the Nurr1-Ret signaling pathway as a target of α-synuclein toxicity and suggest that retinoid X receptor ligands with appropriate pharmacological properties could have therapeutic potential in Parkinson's disease.
These downregulated pathways contained genes known to be transactivated by NR4A2 and were not disrupted in idiopathic PD brain suggesting causality of the mutation.
These findings should stimulate future studies to probe the ligandability and druggability of Nurr1 for both endogenous and synthetic ligands, which could lead to new therapeutics for Nurr1-related diseases, including Parkinson's disease and schizophrenia.
Our approach did not make any assumptions about disease mechanisms, but it, nevertheless, revealed alpha-synuclein, NR4A2 (Nurr1), and the tau genes, which had previously been associated to PD.
The delivery of PLs-GDNF + Nurr1-MBs into the brains using magnetic resonance imaging (MRI)-guided focused ultrasound may be more efficacious for the treatment of PD than the single treatment.
Nurr1 is a member of the nuclear receptor 4 family of orphan nuclear receptors that is decreased in inflammatory responses and leads to neurons death in Parkinson's disease.
"Classic" models are based on neurotoxins that selectively target catecholaminergic neurons (such as 6-hydroxydopamine, 1-methyl-1,2,3,6-tetrahydropiridine, agricultural pesticides, etc.), while more recent models employ genetic manipulations that either introduce mutations similar to those find in familial cases of PD (α-synuclein, DJ-1, PINK1, Parkin, etc.) or selectively disrupt nigrostriatal neurons (MitoPark, Pitx3, Nurr1, etc.).
The orphan nuclear receptor Nurr1 (also known as NR4A2) is critical for the development and maintenance of midbrain dopaminergic neurons, and is associated with Parkinson's disease.
In conclusion, the present study suggests that ABZ exerts a neuroprotective effect in a rotenone-induced PD model associated with HIF-1α and Nurr1 activation and thus may be a viable candidate for treating PD.
Here, we investigated the protective effects of CP on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD in mice and explored the underlying mechanisms of action, focusing on Nurr1.
The aim of this study was to investigate the protective effects of a herbal extract combination, consisting of Bupleurum falcatum, Paeonia suffruticosa, and Angelica dahurica (MABH), on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD-like symptoms and to elucidate possible mechanisms of action focusing on Nurr1.
In order to investigate a possible relation of Nurr1 with the pathogenesis of Parkinson's disease or other neuropsychiatric disorders, we have cloned and characterized the human Nurr1 gene.
Gene-based candidates for Parkinson's disease (PD) include the ubiquitin-proteosome system, scavengers of reactive oxygen species, brain-derived neurotrophic factor (BDNF), its receptor, TrkB, and downstream target early growth response 1, Nurr-1, and signaling through protein kinase C and RAS pathways.