Abstract
BackgroundStress-induced dopaminergic (DAergic) neuronal death in the midbrain region is the primary cause of Parkinson’s disease (PD). Approximately 2% of the global population aged above 65 years is affected with PD. Various factors are responsible for the death of DAergic neurons, among which mitochondrial dysfunction, oxidative stress, misfolded protein aggregation and neuroinflammation are the primary factors. From the discovery of L-dopa, multiple drugs were discovered to improve lifestyle of PD patients, but they failed due to their multiple side effects. Tinospora cordifolia (Tc), a medicinal herb has been used in traditional medicines to treat neurodegenerative diseases. In our previous study, the neuroprotective role of Tc against MPTP-intoxicated Parkinsonian mice was reported. Here, we further explore the neuroprotective molecular mechanisms of Tc in Rotenone (ROT) intoxicated mouse model through proteomics approach.MethodsMice were pretreated with Tc extract by oral administration, followed by ROT-intoxication (2mg/kg body wt. for 35 days, subcutaneous). Rotarod, catalepsy, footprint and pole tests were carried out at 35th day to observe the neuroprotective effects of Tc on motor impairment caused by ROT in PD mice. Protein from nigrostriatal region of the mid brain was isolated, and label free quantification (LFQ) was carried out to identify differentially expressed protein (DEPs) in control vs. PD and PD vs. treatment group. Bioinformatics analysis of DEPs was carried out to explore the molecular pathway, cellular location, molecular function of proteins.ResultsIn this study, we report 800 DEPs in control vs. PD and 133 in PD vs. Treatment group. In silico tools clearly demonstrate significant enrichment of biochemical and molecular pathways with DEPs which are known to be important for PD progression, including, mitochondrial gene expression, hypothetical network for drug addiction, PD pathways, TGF-β signaling, Alzheimer’s disease, Odorant GPCRs and chemokine signaling pathway.ConclusionThis study provides a novel insight for the disease progression in PD mouse. More importantly, it demonstrates that Tc exerts the therapeutic effects through the regulation of multiple pathways to protect DAergic neurons.
Unraveling the Neuroprotective Effect of Tinospora Cordifolia in Parkinsonian Mouse Model Through Proteomics Approach.
