Novel Glitazones Protect Rotenone-induced Parkinsonism in Mouse Models by Targeting PGC1α

Parkinson's disease (PD) is a persistent neurodegenerative condition marked by rising global rates of disability and mortality, warranting the need for new treatment options. The present investigation evaluated the protective effects of novel glitazones C7 and C25 against rotenone-induced PD in a mouse model.

Molecular docking using Discovery Studio and molecular dynamics simulations were employed to evaluate the binding ability of C7 and C25 to the PGC-1α target protein. Pharmacokinetic evaluations of C7 and C25 were performed against the standard pioglitazone in the rats model, and acute toxicity assessments were conducted following OECD guidelines 423. The neuroprotective effects of C7 were tested in a rotenone-induced mouse model of PD at doses of 10, 20, and 30 mg/kg body weight. Behavioral studies, including locomotor activity, grip strength, and catalepsy, as well as biochemical analyses such as endogenous antioxidant levels and AChE levels, were assessed.

The novel compound C7 demonstrated good binding and simulation at the PGC-1α target protein. The kinetic profile of C7 was found to be good when compared to C25. Both the novel glitazones were safe at 300 mg/kg body weight when tested for oral acute toxicity. The novel compound C7 effectively alleviated symptoms related to rotenone-induced PD, demonstrating its promise as a therapeutic candidate.

In the rotenone-induced mouse model, compound C7 exhibited a promising anti-PD effect by attenuating oxidative stress and increasing muscular activity, which merits further investigations.

Additional research using various induction models, along with further investigation of cellular and molecular markers in larger animal studies, is needed to validate these findings.