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.