Nicotine and Other Tobacco Compounds in Neurodegenerative and Psychiatric Diseases

Overview of Epidemiological Data on Smoking and Preclinical and Clinical Data on Nicotine

Emilija Veljkovic, Wenhao Xia, Blaine Phillips, Ee Tsin Wong, Jenny Ho, Alberto Oviedo Casado, Julia Hoeng, Manuel C. Peitsch

• Publisher: Academic Press
• Year: 2018
• Print ISBN: 9780128129227
• eBook ISBN: 9780128129234
• Topic: Biological Sciences
• Subtopic: Medical Theory, Practice & Reference
• Index: Biological Sciences

Nicotine and Other Tobacco Compounds in Neurodegenerative and Psychiatric Diseases: Epidemiological Data on Smoking and Preclinical and Clinical Data on Nicotine provides a comprehensive summary of the epidemiological data on smoking and several neurological disorders, including Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Tourette's syndrome, schizophrenia, anxiety, depression and ADHD, as well as preclinical and clinical data on the effects of nicotine. Despite the obvious and undisputed harmful nature of smoking, evidence suggests that some tobacco and tobacco smoke-derived constituents may offer neuroprotective effects, possibly in combinations, rather than individually.This unprecedented book describes the complex relationships between smoking and neurological disease and the bioactive compounds found in tobacco. It provides a comprehensive review of nicotine and other compounds found in tobacco plant, with scientific evidence of neuroprotective and anti-inflammatory effects that may act in conjunction with nicotine to exert neuroprotective effects observed in smokers.By presenting findings beyond harmful cigarette smoke effects, attention can be drawn to individual compounds of tobacco that may serve as inspiration for further therapy development.- Presents the first comprehensive, tabulated summary of literature on the epidemiological data on smoking and neurological disease- Includes preclinical and clinical data on nicotine in neurological diseases and mechanisms of action of nicotine in neuroprotection- Features a comprehensive summary of non-nicotine smoke constituents with potentially neuroprotective and anti-inflammatory properties- Discusses Multiple Sclerosis, Alzheimer's disease, Parkinson's Disease, Schizophrenia, Depression, ADHD, Anxiety and Tourette's Syndrome in the context of smoking and nicotine

Part I

Overview of Epidemiological Data on Smoking and Preclinical and Clinical Data on Nicotine

Chapter 1

Parkinson's Disease

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects movement. This motor deficit is due to the loss of dopaminergic neurons in the substantia nigra pars compacta. In this chapter, the inverse correlation between smoking and snus consumption and the incidence of Parkinson's disease (PD) are discussed. Nicotine was a topic of preclinical and clinical investigations into its therapeutic potential because nicotine stimulates dopamine release, a property relevant to PD. Clinical data were inconclusive, with some positive and some negative results following administration of nicotine via different routes. Given the roles of different nAChRs in PD, nicotine should be investigated further for its pharmacological properties. The inconsistency between epidemiological data and clinical trial results obtained with nicotine alone may suggest that other tobacco compounds, separated from combustible tobacco products, may play a role.

Keywords

Parkinson’s disease; Nicotine; nAChRs; Snus; Dopamine

1.1 Symptoms and Epidemiology

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects movement. Early signs may be mild and go unnoticed. Symptoms often begin on one side of the body and usually remain worse on that side, even after both sides have been affected. These motor deficits are due to the loss of dopaminergic neurons in the substantia nigra pars compacta.^39,40 Although the deficit in this brain region is the most severe, other neurotransmitter systems are affected, and these most likely underlie the autonomic problems, cognitive decline, changes in affect, and sleep disturbances.²²

Approximately 1% of individuals older than 60 years are affected by PD, but younger people can also develop PD. Around 60,000 Americans are diagnosed with PD each year, yet this number does not reflect the thousands of cases that go undetected. It has been estimated that 7–10 million people worldwide are living with PD.⁴¹ The incidence of PD increases with age, but an estimated 4% of PD patients are diagnosed before the age of 50. In the United Kingdom, 1 person in every 500 has PD, with prevalence ranging from 105 to 178 persons with PD per 100,000 population, after adjusting for age.⁴²

1.2 Molecular Mechanisms

The etiology of PD is not completely understood and has been attributed to a complex interplay between genetic and environmental factors. Each of these factors conveys increased risk of disease. A minority of cases (approximately 5%) are genetic (familial), displaying Mendelian inheritance, while the rest are sporadic cases.⁴³ The pathogenesis of PD involves multiple, related processes including mitochondrial dysfunction, oxidative and nitrative stress, microglial activation, inflammation, aggregation of α-synuclein, and impaired autophagy.^44–46 For many of these factors, the question of whether they are causative or consequential remains open, and they are probably both.

Clinical symptoms appear when around 70% of the dopaminergic neurons in the substantia nigra pars compacta are lost. Clinical, neuropathologic, and neuroimaging findings suggest that the neurodegenerative process of PD begins many years before the onset of motor manifestations. More recent or ongoing studies are largely devoted to the identification of potential markers for the preclinical, or at least premotor stage of the disease, in which dopaminergic neurons are relatively spared and neuroprotective treatments may have a potential effect.⁴⁷ Although the precise mechanisms of PD pathogenesis are only partially understood, it is now widely accepted that the accumulation and aggregation of α-synuclein, a principal component of Lewy pathology, plays a crucial role in the pathogenesis of familial and sporadic PD.⁴⁸ The precise reason why Lewy bodies develop is not known, and it appears that the Lewy pathology is neither the first sign nor the prerequisite for PD development.⁴⁹ Alpha-synuclein may contribute to PD pathogenesis in a number of ways, but it is generally thought that its aberrant soluble oligomeric conformations are the toxic species that mediate disruption of cellular homeostasis and neuronal death, through effects on various intracellular targets, including synaptic function. Furthermore, secreted α-synuclein may exert deleterious effects on neighboring cells, including seeding of aggregation, thus possibly contributing to disease propagation. Accumulated α-synuclein was also found in patients with other neurodegenerative conditions, collectively termed “synucleinopathies.”

Based on the literature and current clinical practices, the main therapy for PD is dopamine replacement. This provides effective motor symptom control, particularly in the early disease stage. As the pathology progresses and various nonmotor deficits occur, dopamine replacement does not adequately manage the disease symptoms. In addition, dopamine replacement induces a variety of motor and psychiatric side effects. In May 2006, the Food and Drug Administration (FDA) approved rasagiline to be used with lev...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Disclaimer
• Acknowledgments
• Foreword
• Introduction
• Search Methods
• Part I: Overview of Epidemiological Data on Smoking and Preclinical and Clinical Data on Nicotine
• Part II: Overview of the Pharmacology of Nicotine and Other Tobacco-Derived Compounds
• Abbreviations
• References
• Index