Activation of Nrf2 neuroprotective pathways for treatment of Parkinson's disease: A state of art review.

The regulation of Nuclear Factor-Erythroid 2 Like 2 (NRF2) signaling has been shown to be a promising strategy to modulate the progression of the neurodegeneration associated to Parkinson's Disease (PD). Aim of this review is to update the knowledge of Nrf2 as neuroprotective agent of PD. Activation of Nrf2, a transcription factor that regulates the expression of antioxidant and cytoprotective genes, has emerged as a promising therapeutic strategy for PD. Nrf2 is a master regulator of the cellular antioxidant response and is responsible for activating the expression of genes that encode antioxidant enzymes such as superoxidedismutase, catalase, and glutathione peroxidase. Pharmacological agents such as sulforaphane, curcumin, and resveratrol have been shown to activate Nrf2 and upregulate the expression of antioxidant genes in preclinical PD models. Clinical trials are currently underway to evaluate the efficacy of these pharmacological agents in patients with PD. While the neuroprotective role of Nrf2 in PD holds great promise for the development of novel therapies, there are several challenges and limitations that need to be addressed in order to harness the full potential of this pathway in the clinic. Overcoming these obstacles will require interdisciplinary collaborations, innovative research approaches, and a greater understanding of the complex pathophysiology of PD. By addressing these challenges, we can move closer to developing effective neuroprotective therapies that can slow or stop the progression of PD and improve the quality of life for patients with this devastating disease.