Effect of nicotine on the energy metabolism of substantia nigra cells in mptp-induced Parkinson’s disease

Articles in Press

Document Type : Original Article

Authors

1 Department of Biology, Faculty of Exact and Natural Sciences, Iv. Javakhishvili Tbilisi State University, Tbilisi, Georgia

2 Faculty of Medicine, Iv. Javakhishvili Tbilisi State University, Tbilisi, Georgia

10.22038/ijbms.2025.84754.18338

Abstract

Objective(s): Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions globally, with no current cure despite extensive research efforts. The neurotoxin MPTP is commonly used as a PD model by inhibiting mitochondrial complex I. Nicotine, the primary alkaloid in tobacco, has shown potential neuroprotective effects against neurodegenerative diseases, including PD, although the precise mechanisms remain unclear. This study aims to investigate the effects of nicotine on the energetic metabolism of substantia nigra cells affected by MPTP.
Materials and Methods: We examined the impact of nicotine on glycolytic, Krebs cycle, and respiratory chain enzymes in substantia nigra cells, as well as mitochondrial and cytosolic creatine kinase activities. ATP levels, mitochondrial permeability transition pore (mPTP) activity, and PI3K-AKT-mTOR signaling pathway were also assessed. The study was performed on a mouse model where PD was induced by MPTP, followed by nicotine treatment.
Results: Nicotine administration led to improvements in mitochondrial function, with enhanced ATP production, creatine kinase activity, and overall energetic metabolism. Nicotine corrected the energetic deficiencies induced by MPTP, likely through the activation of the PI3K-AKT-mTOR pathway, which is suppressed by MPTP.
Conclusion: Our findings suggest that nicotine may exert neuroprotective effects in Parkinson’s disease by improving mitochondrial function and enhancing energetic metabolism, potentially via activation of the PI3K-AKT-mTOR pathway. This highlights nicotine’s potential as a therapeutic agent in mitigating PD-induced metabolic disturbances.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

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Available Online from 09 July 2025

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