Unraveling the Neuroprotective Effect of Tinospora cordifolia in a Parkinsonian Mouse Model through the Proteomics Approach
| Autor: | Aaina Singh Rathore, Hareram Birla, Walia Zahra, Monika Rajput, Hagera Dilnashin, Surya Pratap Singh, Richa Singh, Saumitra Sen Singh, Chetan Keswani, Priyanka Kumari Keshri |
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| Rok vydání: | 2021 |
| Předmět: |
Parkinson's disease
biology Physiology business.industry Cognitive Neuroscience Dopaminergic Cell Biology General Medicine Rotenone Pharmacology Tinospora cordifolia biology.organism_classification medicine.disease Proteomics Biochemistry Neuroprotection Proinflammatory cytokine Label-free quantification chemistry.chemical_compound chemistry medicine business |
| Zdroj: | ACS Chemical Neuroscience. 12:4319-4335 |
| ISSN: | 1948-7193 |
| Popis: | Stress-induced dopaminergic (DAergic) neuronal death in the midbrain region is the primary cause of Parkinson's disease (PD). Following the discovery of l-dopa, multiple drugs have been developed to improve the lifestyle of PD patients; however, none have been suitable for clinical use due to their multiple side effects. Tinospora cordifolia has been used in traditional medicines to treat neurodegenerative diseases. Previously, we reported the neuroprotective role of Tc via inhibition of NF-κB-associated proinflammatory cytokines against MPTP-intoxicated Parkinsonian mice. In the present study, we investigated the neuroprotective molecular mechanism of Tc in a rotenone (ROT)-intoxicated mouse model, using a proteomics approach. Mice were pretreated with Tc extract by oral administration, followed by ROT intoxication. Behavioral tests were performed to check motor functions of mice. Protein was isolated, and label-free quantification (LFQ) was carried out to identify differentially expressed protein (DEP) in control vs PD and PD vs treatment groups. Results were validated by qRT-PCR with the expression of target genes correlating with the proteomics data. In this study, we report 800 DEPs in control vs PD and 133 in PD vs treatment groups. In silico tools demonstrate significant enrichment of biochemical and molecular pathways with DEPs, which are known to be important for PD progression including mitochondrial gene expression, PD pathways, TGF-β signaling, and Alzheimer's disease. This study provides novel insights into the PD progression as well as new therapeutic targets. More importantly, it demonstrates that Tc can exert therapeutic effects by regulating multiple pathways, resulting in neuroprotection. |
| Databáze: | OpenAIRE |
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