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.
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).
Our aim was to evaluate the influence of NR4A2 gene in the performance of schizophrenia (SZ) patients and healthy subjects on a sustained attention task.
Evidence by others support this hypothesis (1) mapping of the NR4A2 gene to chromosome 2q22-23, a region with suggestive linkage to schizophrenia and (2) identification of mutations in patients with schizophrenia (c.366-369delTAC, c.308A > G, c.-469delG), manic depression (c.289A > G), and familial Parkinson's disease (c.-291delT, c.-245T > G).
We conclude that the identified polymorphic sites in the human NURR1 are unlikely to be involved in conferring susceptibility for SZ or PD in our patient material.
The result suggests that the c.-469delG and possibly other variants of the NR4A2 gene may be of relevance to the complex factors involved in the pathogenesis of schizophrenia.
Further analysis of the polymorphism of the human Nurr1 gene may reveal the association with diseases characterized by changes of the DA system, such as Parkinson's disease and schizophrenia.