Mechanistic insights into the role of nuclear receptor related-1 protein in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic (DA) neurons in the brain resulting in motor and cognitive deficits. Among the key molecular regulators implicated in PD, the nuclear receptor-related-1 protein (Nurr1) has emerged as an important transcription factor involved in the growth, maintenance, and survival of DA neurons in PD. It regulates genes involved in dopamine production, neuronal differentiation, and neuroprotection. Beyond its classical neurodevelopmental functions, recent findings reveal that Nurr1 exerts potent anti-inflammatory effects by suppressing pro-inflammatory gene expression in glial cells, thereby mitigating neuroinflammation-a key pathological hallmark of PD. Dysregulation or downregulation of Nurr1 compromises mitochondrial function, anti-oxidant defense, and neuronal viability, rendering the brain more vulnerable to oxidative stress and neuroinflammation. Therefore, this review highlights the Nurr1 crucial involvement in the pathophysiology of PD, including its regulatory actions in DA neurobiology and neuroinflammation. We also describe the various molecular signaling pathways that modulate the role of Nurr-1 in PD, current treatment techniques for manipulating Nurr1 function and epigenetic and post-translational modifications of Nurr1, emphasizing its potential as a novel target for PD therapies.