Beneficial effects of nicotine, cotinine and its metabolites as potential agents for Parkinson's disease.

George E. Barreto,Valentina Echeverria Moran,Alexander Iarkov

doi:10.3389/fnagi.2014.00340

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, which is characterized by neuroinflammation, dopaminergic neuronal cell death and motor dysfunction, and for which there are no proven effective treatments. The negative correlation between tobacco consumption and PD suggests that tobacco-derived compounds can be beneficial against PD. Nicotine, the more studied alkaloid derived from tobacco, is considered to be responsible for the beneficial behavioral and neurological effects of tobacco use in PD. However, several metabolites of nicotine, such as cotinine, also increase in the brain after nicotine administration. The effect of nicotine and some of its derivatives on dopaminergic neurons viability, neuroinflammation, and motor and memory functions, have been investigated using cellular and rodent models of PD. Current evidence shows that nicotine, and some of its derivatives diminish oxidative stress and neuroinflammation in the brain and improve synaptic plasticity and neuronal survival of dopaminergic neurons. In vivo these effects resulted in improvements in mood, motor skills and memory in subjects suffering from PD pathology. In this review, we discuss the potential benefits of nicotine and its derivatives for treating PD.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative illness after Alzheimer’s disease (AD), and reaches a prevalence of 3% after 65 years of age (Jellinger, 2003)
Parkinson’s disease is characterized by the presence of Lewy bodies, mainly composed of alpha-synuclein fibrils, a depletion of dopamine (DA)-generating neurons in substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) regions of the brain (Wirths and Bayer, 2003; Dexter and Jenner, 2013), that results in a decrease of DA levels in the striatum and frontal cortex regions of the brain
Since behavioral sensitization would be dependent on the activation of DA systems, and nornicotine evokes DA release, these results suggest a significant role for nornicotine in the behavioral sensitization produced by nicotine

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative illness after Alzheimer’s disease (AD), and reaches a prevalence of 3% after 65 years of age (Jellinger, 2003). This evidence further supported the view that the neuroprotective effects of nicotine were the result of nAChRs stimulation, which promotes DA release and increases the survival of dopaminergic neurons by activating anti-apoptotic factors. These treatments significantly improved striatum integrity and basal DA release from lesioned striatum, as well as nicotine-stimulated DA release mediated via α4β2 and α6β2 nAChRs. In summary, epidemiological studies consistently have shown a lower risk of PD among smokers suggesting that this association is causal (Mellick et al, 2006; O’Reilly et al, 2009).

Results

Conclusion