Abstract

Parkinson’s disease (PD) is amongst the most common hypokinetic conditions, which is manifested via the gradual deterioration of nigral dopamine-expressing neurons, causing a reduction in the content of dopamine. Ang (1–7), a vasoprotective heptapeptide of the renin-angiotensin system, exerts neuroprotection against PD in various experimental conditions. Additionally, Ang (1–7) ameliorates the oxidative stress in Parkinson’s models. The study aimed to investigate how Ang (1–7) prevents rotenone-induced PD-like symptoms in rats and to evaluate the contribution of the Mas receptor and Nrf2 signaling pathways using A779, a Mas receptor antagonist, and Trigonelline, an Nrf2 inhibitor, respectively. Daily administration of Ang (1–7) was conducted for fourteen days, with or without A779 and Trigonelline. Behavioral analysis was performed on the last day. Biochemical parameters related to dopamine and mitochondrial functions were assessed. Ang (1–7) alleviated the effects of rotenone-induced alterations in behavioral functions, measured by narrow beam walk, open field, rotarod, bar catalepsy, grip strength, footprint, and actophotometer tests. Parameters such as dopamine levels and mitochondrial functions were restored after treatment with Ang (1–7) in rotenone-challenged rodents. The compounds A779 and Trigonelline counteracted the therapeutic benefits of Ang (1–7) in rats exposed to the neurotoxin rotenone. Following Ang (1–7) administration, both behavioral and biochemical assessments improved in rotenone-induced Parkinson-like symptoms. Therefore, Ang (1–7)/MasR/Nrf2 signaling could serve as an adjunct in the pharmacotherapy of PD.

Key words: Parkinson’s disease; Ang (1-7)/MasR/Nrf2; Rotenone, Dopamine, Mitochondrial dysfunctions.