Development of Alpha-Synuclein protein model against therapeutic aspects of Parkinson's disease.

JOURNAL/ijpha/04.03/01363791-202456010-00007/figure1/v/2024-03-07T095025Z/r/image-tiff Parkinson's disease (PD) is the most common neurodegenerative disease caused by the steady depletion of dopamine in the striatum due to the loss of dopaminergic neurons. Most of the current therapeutics work on rebuilding the striatal dopamine level through oral administration of levodopa which stops the symptoms of PD. But there is a long-term motor complication with these dopamine precursors. Moreover, no preventive treatment is available for PD. Thus, before finding a therapeutic treatment for PD, it is necessary to first understand the basic cause of PD. Moreover, alpha-synuclein oligomerization can be the major factor in PD. From the UniProt database, protein information was extracted, and the model was designed by homology modeling technique and validated by the model validation server. Hence, the designed model has 96.5% most favored region and 0% disallowed region. Therefore, the model is stable based on RC plot parameters.

Effect of ß-cyfluthrin (synthetic pyrethroid) on learning, muscular coordination and oxidative stress in Swiss albino mice.

The present study was planned to evaluate neurotoxic effects of ß-cyfluthrin in female Swiss albino mice. Two doses of ß-cyfluthrin, specifically, one-tenth of median lethal dose (LD50) and one-twentieth of LD50, were selected for the study. Open-field behaviour, exploratory behaviour and emotional status were affected, and animals showed anxiety-like behaviour after ß-cyfluthrin administration. Spatial learning was decreased using the Hebb-Wiliams maze. Acetylcholinesterase enzyme activity significantly decreased in the treated animals. The administration of ß-cyfluthrin caused increased lipid peroxidation (malondialdehyde) and decreased superoxide dismutase, catalase and glutathione peroxidase activity in brain tissue. In conclusion, ß-cyfluthrin caused neurotoxicity as well as oxidative damage in the brain of Swiss albino mice at the tested dose levels.

Curcumin modulates oxidative stress and genotoxicity induced by a type II fluorinated pyrethroid, beta-cyfluthrin.

Present study examines the possibility of ß-cyfluthrin (ß-CYF) induced oxidative stress, genotoxicity, histopathological alterations and the role of curcumin (CUR) in alleviating its toxic effects. CUR is a naturally occurring phenolic compound of turmeric (Curcuma longa) and is used as a spice, food-coloring agent and in cosmetics and medicines. CUR provides vital protection against many pathological conditions due to its antioxidant and anti-inflammatory properties. Male Swiss albino mice were distributed into six groups, I: control, II: CUR (0.2%), III: ß-CYF low dose (1/20 of LD50), IV: ß-CYF high dose (1/10 of LD50), V: ß-CYF low dose + CUR and VI: ß-CYF high dose + CUR. Mice were orally administered their respective doses daily for 21 days. ß-CYF caused elevation in AST, ALT, LPO and decline in GPx, CAT and SOD activities. A significant decrease in MI and increase in chromosomal aberrations, TL, TI and TM was recorded in ß-CYF exposed groups. CUR co-administration modulated AST, ALT, LPO, GPx, CAT and SOD activity. CUR supplementation improved the MI and reduced the chromosomal aberrations, TL, TI and TM. ß-CYF caused serious pathological alterations in liver and these were alleviated by CUR. It is concluded that CUR scavenges ROS and renders a protection against ß-CYF genotoxicity.