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

What is your doctors' take on beneficial effects for stroke? I've only written 18 posts on it.
http://journal.frontiersin.org/article/10.3389/fnagi.2014.00340/full?
Don't prescribe smoking for yourself.
George E. Barreto^1*, Alexander Iarkov^2,3 and Valentina Echeverria Moran^2,3,4,5*

• ¹Department of Nutrition and Biochemistry, Pontificia Universidad Javeriana, Bogotá, D. C., Colombia
• ²Center of Research in Biomedical Sciences, Universidad Autónoma de Chile, Santiago, Chile
• ³Research & Development Service, Bay Pines VA Healthcare System, Bay Pines, FL, USA
• ⁴Research Service, James A Haley Veterans’ Hospital, Tampa, FL, USA
• ⁵Department of Molecular Medicine, Morsani College of Medicine, University of South, Tampa, FL, USA

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.

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). Parkinson’s disease is predominantly sporadic, and rarely familial. The familial form of the disease can develop due to single genetic mutations (Dexter and Jenner, 2013). 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 (Thompson et al., 2005). Parkinson’s disease affects cognitive and motor abilities (Riedel et al., 2014), and progressively impairs sleep (Dos Santos et al., 2014), attention, and short-term memory, as well as visuospatial and executive functions (Liu et al., 2012; Conte et al., 2013; Rottschy et al., 2013; Zokaei et al., 2014). The dopaminergic deficit observed in PD patients seems to underlie the motor impairment symptoms such as hypokinesia, tremor and rigidity (Murer and Moratalla, 2011).

The cause of death of dopaminergic neurons is still a mystery; however, actual evidence is consistent with the idea that oxidative stress, mitochondrial dysfunction and neuroinflammation are the main factors involved in the etiology of PD (Büeler, 2010; Zuo and Motherwell, 2013; Camilleri and Vassallo, 2014; Celardo et al., 2014). It has been proposed that various genetic and environmental factors causing mitochondrial dysfunction result in abnormal accumulation of miscoded proteins and the generation of oxidative stress in the brain of subjects with PD (Bové and Perier, 2012; Cabezas et al., 2012, 2014; Perier and Vila, 2012; Dexter and Jenner, 2013; Trinh and Farrer, 2013; Zuo and Motherwell, 2013; Figure 1).