Activation of Nrf2 Neuroprotective Pathways for Treatment of Parkinson’s Disease: A State of Art Review

(1) Background: Since there is no definite cure for Parkinsons Disease (PD) there is a growing interest for novel therapeutical agents with neuroprotective potential. Aim of this review is to update the knowledge of nuclear factor-erythroid 2-related factor 2(Nrf2) as neuroprotective agent ; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: 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 superoxide dismutase, catalase, and glutathione peroxidase. These enzymes help to neutralize ROS and protect cells from oxidative damage. Nrf2 also regulates the expression of genes involved in the detoxification of harmful substances and the repair of damaged DNA. In addition to its antioxidant and cytoprotective functions, Nrf2 has been shown to have anti-inflammatory properties that can help to alleviate the neuroinflammation associated with PD. 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 . These compounds work by disrupting the interaction between Nrf2 and its negative regulator, Keap1, leading to the translocation of Nrf2 into the nucleus where it can activate the expression of cytoprotective genes. Clinical trials are currently underway to evaluate the efficacy of these pharmacological agents in patients with PD. (4) Conclusions: 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.