A novel protective modality against rotenone-induced Parkinson's disease: A pre-clinical study with dulaglutide

Parkinson's disease (PD) drugs treat symptoms without inhibiting progression. In recent years, finding novel therapeutic medications that can halt disease progression has become crucial. Research on antidiabetic medicines is valuable in these investigations because of the parallels between the two disorders. Using Rotenone (ROT), a frequently used PD model, the possible neuroprotective benefits of Dulaglutide (DUL), an extended-acting glucagon-like peptide-1 agonist, were considered. Twenty-four rats were randomly assigned to 4 groups to complete this experiment (n = 6). 0.2 ml of the vehicle (1 ml of dimethyl sulfoxide (DMSO) diluted in sunflower oil) was administered to the standard control group subcutaneously with a 48-hour pause. The second group was administered ROT 2.5 mg/kg SC every 48 h for 20 days as a positive control group. The third and fourth groups were administered one dose of DUL each week (0.05 and 0.1 mg/kg SC, respectively) to their regimens. The mice received ROT (2.5 mg/kg SC) every 48 h for 20 days after receiving DUL for the initial dose (96 h later). The current study focused on the DUL's ability to preserve usual behavioral function, enhance antioxidant and anti-inflammatory pathways, inhibit alpha-synuclein (α-syn), and increase parkin levels. It is concluded that DUL acts as an antioxidant and an anti-inflammatory to protect against ROT-induced PD. However, more studies are required to support this finding.