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Neuromodulation in Parkinson’s disease targeting opioid and cannabinoid receptors, understanding the role of NLRP3 pathway: a novel therapeutic approach

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Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor and non-motor symptoms. Although levodopa is the primary medication for PD, its long-term use is associated with complications such as dyskinesia and drug resistance, necessitating novel therapeutic approaches. Recent research has highlighted the potential of targeting opioid and cannabinoid receptors as innovative strategies for PD treatment. Modulating opioid transmission, particularly through activating µ (MOR) and δ (DOR) receptors while inhibiting κ (KOR) receptors, shows promise in preventing motor complications and reducing L-DOPA-induced dyskinesia. Opioids also possess neuroprotective properties and play a role in neuroprotection and seizure control. Similar to this, endocannabinoid signalling via CB1 and CB2 receptors influences the basal ganglia and may contribute to PD pathophysiology, making it a potential therapeutic target. In addition to opioid and cannabinoid receptor targeting, the NLRP3 pathway, implicated in neuroinflammation and neurodegeneration, emerges as another potential therapeutic avenue for PD. Recent studies suggest that targeting this pathway holds promise as a therapeutic strategy for PD management. This comprehensive review focuses on neuromodulation and novel therapeutic approaches for PD, specifically highlighting the targeting of opioid and cannabinoid receptors and the NLRP3 pathway. A better understanding of these mechanisms has the potential to enhance the quality of life for PD patients.

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Acknowledgements

Authors pay deep sense of gratitude to Prof. (Dr.) Y.K. Gupta (MD, PhD) President AIIMS Bhopal and Jammu and Chairman Research Advisory committee ISF College of Pharmacy, Moga-142001, Pb. India. Further highly thankful to management and chairman Sh. Parveen Sir, ISF College of Pharmacy, Moga-142001, Pb. India and all those scientists who published lot of advanced research in the field of Neuropharmacology.

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  1. Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India

    Md Reyaz Alam & Shamsher Singh

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MRA wrote the manuscript, manuscript reading, data collection and data contribution. SS contributed as designed review paper, data analysis, manuscript reading and final approval.

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Alam, M.R., Singh, S. Neuromodulation in Parkinson’s disease targeting opioid and cannabinoid receptors, understanding the role of NLRP3 pathway: a novel therapeutic approach. Inflammopharmacol 31, 1605–1627 (2023). https://doi.org/10.1007/s10787-023-01259-0

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