DACA alleviates nerve damage and motor dysfunction via activation on Nrf2 signaling in Parkinson's disease.

Abstract

Background and Purpose Parkinson’s disease (PD) is the fastest growing neurological disorder. Strong evidence reveals that oxidative stress and mitochondrial dysfunction play critical roles in the pathophysiology of PD. Rosemary contains a large number of abietane diterpenoids with antioxidant power and DACA is a modified product from it. The present study revealed the anti-parkinsonian effects of DACA and its possible mechanisms. Experimental Approach The PD model was established by treating mice with MPTP and SH-SY5Y cells and primary neurons with MPP+. western blot and immunofluorescence were used to evaluate the neuroprotective effect of DACA. At the same time, the anxiety-like behavior and motor coordination ability of mice were detected. In addition, reactive oxygen species (ROS) detection, mitochondrial membrane potential detection and western blot were used to detect oxidative stress and mitochondrial related signal changes. Key Results DACA improved the motor dysfunction of mouse and inhibited the decrease of tyrosine hydroxylase (TH) positive neurons in substantia nigra (SN) and TH protein expression in midbrain and striatum. It also enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant enzymes in midbrain and striatum. DACA prevented MPP+- induced toxicity, reduced oxidative stress and maintained mitochondrial function. The neuroprotective effects of DACA were associated with its ability to induce Nrf2 into nucleus and regulate mitophagy. Conclusion and Implications In conclusion, we demonstrated that DACA exerted significant neuroprotection against through the regulation of Nrf2 signaling, suggesting the use of DACA as a possible food supplement in the prevention of PD.