Novel glitazone attenuates rotenone-induced toxicity in mouse model of Parkinson’s disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder, and there are no drugs that will directly tackle the inflammatory component of PD. In the present study, we assessed the novel glitazone for reversal of rotenone-induced toxicity in experimental mouse model. The 14 virtual glitazone compounds were subjected to molecular docking study for target protein 3CS8; among these, compound C25 and C34 have shown better binding activity. Pharmacokinetics studies were conducted for the above compounds in rat model to chose best one for further toxicity and efficacy studies. The compound C25 showed better kinetic profile when compared to C34 and better t 1/2 when compared to the standard pioglitazone. Compound C25 then tested for acute toxicity by OECD guideline 423 and evaluated for its neuroprotective activity in mouse model. The activity of the compound was assessed by the behavioral parameters on weekly intervals during the study period and estimated the antioxidant level in the brain homogenate. The compound has shown good activity dose-dependently; however, further research is required to confirm its activity and to support our hypothesis.

Toxoplasma Reduces Complications of Parkinson’s Disease: An Experimental Study in BALB/c Mice

“…Rats and different mouse models such as C57BL/6N have been applied as animal models to PD induction in previous studies [18,25,26]. Similar to other studies, the current study indicates using rotenone; BALB/c mouse can be also considered as an appropriate animal model for PD induction [27,28]. Since T. gondii genotype I is lethal in mice and not an appropriate strain in our study, the PRU-II strain was used for induction of chronic toxoplasmosis.…”

Uncovering Novel Therapeutic Targets for Parkinson’s Disease

“…3CI-TZD-3,4,5-trimethoxy­benzaldehyde (C25) also ameliorated toxic effects induced by neurotoxin rotenone. It demonstrated good binding to PGC-1α-PPAR-γ in docking studies . Interestingly, it was found that PPAR- β/δ agonist can also provide neuroprotective actions.…”

“…It demonstrated good binding to PGC-1α-PPAR-γ in docking studies. 90 Interestingly, it was found that PPAR-β/ δ agonist can also provide neuroprotective actions. PPAR-β/δ agonists, L-165041, and GW-501516 were able to protect SH-SY5Y cells from neurotoxicity induced by MPP+ by interfering with caspase-3 signaling cascade.…”