Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 155, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2021.112433
Keywords
Unfolded protein response; Endoplasmic reticulum stress; Neuronal communication
Categories
Funding
- Science and Engineering Research Board [PDF/2017/000984]
- Indian Council of Medical Research [20160264/CMB/AdhocBMS]
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This study demonstrates that resveratrol can interfere with neuronal communication, oxidative stress, mitochondrial pathophysiology, ER stress, protein degradation mechanism, and inflammatory responses in the context of Parkinson's disease, suggesting its potential clinical utility for treating PD patients.
The present study was undertaken to evaluate the mechanism for antiParkinsonian effect of resveratrol employing 6-hydroxydopamine (6-OHDA) induced experimental model of Parkinson's disease (PD). Resveratrol treatment significantly protects the PD related pathological markers like level of tyrosine hydroxylase, dopamine and apoptotic proteins (Bax and cleaved caspase-3). Disease pathology involves significantly decreased level of dopamine transporter, synaptophysin and postsynaptic density protein 95 (PSD-95) along with augmented level of vesicular monoamine transporter and considerably affected the dendrite arborization. Such affected neuronal communication was significantly restored with resveratrol treatment. Biochemical alterations include the depleted level of glutathione (GSH), mitochondrial complex-I activity with concomitant increased level of lipid peroxidation, nitrite level and calcium levels, which were also significantly inhibited with resveratrol treatment. Altered calcium level induces the endoplasmic reticulum (ER) stress related signalling and phosphorylated Nuclear factor erythroid 2-related factor 2 (Nrf2), and with resveratrol treatment the level of phosphorylated Nrf2 was further increased. The concurrent depleted level of proteasome activity was observed which was attenuated with resveratrol treatment. Proinflammatory cytokines and activated astrocytes were observed which was inhibited with resveratrol treatment. In conclusion, findings suggested that resveratrol exhibits the interference in neuronal communication, oxidative stress, mitochondrial pathophysiology, ER stress, protein degradation mechanism and inflammatory responses and could be utilize in clinics to treat the PD patients.
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