Parkinson's Disease Therapeutics

Emphasis on Nanotechnological Advances

Magisetty Obulesu

• Publisher: Academic Press
• Year: 2020
• Print ISBN: 9780128198827
• eBook ISBN: 9780128198834
• Topic: Medicine
• Subtopic: Physiology

Parkinson's Disease Therapeutics: Emphasis on Nanotechnological Advances presents the latest information on the second most common neurodegenerative disorder in the elderly. Despite remarkable progress in various PD therapeutics, such as microRNAs and brain drug delivery systems, a few limitations impede their success. This book sheds light on the pros and cons of recently developed novel therapeutics. Very few books have highlighted the protective efficacy of natural products, antioxidants, and biomaterial design for other diseases.- Emphasizes novel therapeutics for Parkinson's disease, including nanotechnology, natural products and antioxidants- Discusses the pros and cons of recently developed therapy options for Parkinson's- Focuses on the efficacy of nanotechnology in overcoming the blood-brain barrier and biomaterial design

Chapter 1

Introduction

Parkinson's disease pathology and therapeutics

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder in the elderly. Vital pathological events include decline in nigrostriatal neurons and deterioration of neurotransmitter dopamine. As amyloid fibrils are the key end products of several proteins implicated in neurodegenerative diseases, panoply of studies emphasize their diagnosis as the mainstay of current research. Despite remarkable progress in multifarious PD therapeutics such as micro-RNAs and brain drug delivery systems, a few limitations impede their success. In addition, hitherto employed nanotechnological therapeutic avenues for brain diseases have not been more effective strategies as they are for other diseases. Therefore, this chapter throws light on advantages and disadvantages of recently developed novel therapeutics.

Keywords

Drug delivery systems; Drugs; Liposomes; Micro-RNAs; Nanotechnology; Parkinson's disease; Viral vectors

1. Introduction

1.1. Pathology

Parkinson's disease (PD) has been considered the second most common neurodegenerative disease after Alzheimer's disease (AD) since its identification by the English physician James Parkinson in 1817 (Pringsheim et al., 2014; Gao et al., 2019). Reactive oxygen species (ROS) generation, oxidative stress, apoptosis, genetic mutations, and metal intoxication have long been implicated in the etiology of neurodegenerative diseases such as AD and PD (Obulesu et al., 2009, Obulesu and Muralidhara Rao, 2010, 2011a,b, Obulesu and Jhansilakshmi, 2014a,b, 2016 , Obulesu, 2018). PD is the most common neurodegenerative disorder in the elderly. The prevalence of PD is about 1 in every 100 people over 65 years age (Siddiqi et al., 2018). The prominent pathological characteristics involved in PD are formation of amyloid protein fibrils, deterioration of neurotransmitter, and dopamine (DA) (Mohammadi and Nikkah, 2017). As DA actively plays a role in electric signal transmission, which is important in normal physical movement, its low levels result in bradykinesia, rigidity, and resting tremor (Ramanathan et al., 2018). In addition, pathological Lewy bodies are initially observed in brain stem and olfactory bulb, which further extend to cortex and nigra (Ramanathan et al., 2018). PD patient's brain showed low levels of astroglial cells because of the downstream processing in brain (Orr et al., 2002; Mena, 2008; Obeso et al., 2010 , Ramanathan et al., 2018).

2. Micro-ribonucleic acid

Micro-ribonucleic acid (miRNA), which is small noncoding RNA, plays a pivotal role in posttranscriptional gene silencing. Abnormal expressions of miRNA have long been implicated in neurodegenerative disorders such as PD (Hebert and De Strooper, 2009, Titze de Almeida et al., 2018). Antisense single-stranded oligos (AntimiRs) were found to reverse rotenone-induced damage in dopaminergic SH-SY5Y cells (Horst et al., 2017, Titze de Almeida et al., 2018). In line with this, intracerebroventricular injection of AntimiRs into rat brain probably protects striatum, which is usually involved in PD pathology (Titze de Almeida et al., 2018).

3. Drugs

Levodopa has been extensively used drug in the treatment of PD. However, it poses a few biological riddles such as gastric pH; intervention of proteins with bioavailability of drugs limits the success of drugs (Ramanathan et al., 2018). Rotigotine exhibits neuroprotection by improving motor symptoms in PD (Fig. 1.1) (Stockwell et al., 2010; Yu et al., 2015; Yan et al., 2018a,b). Rotigotine patch comprises drug in elastic vessels and released in silicon matrix via ionic gradients resulting in equal distribution in the epidermis (Johnston et al., 2005; Katzenschlager et al., 2005; Nyholm et al., 2005; Bennet and Piercy, 1999 , Ramanathan et al., 2018). Despite the lipophilicity of the drugs, their efflux has frequently been observed because of the occurrence of multispecific organic anion transporter (MOAT), P-glycoprotein (Pgp), and multidrug resistance proteins (MRPs) (Hans and Lowman, 2002; Persidsky et al., 2006, Ramanathan et al., 2018).

Figure 1.1 Multifarious therapeutic avenues targeted against Parkinson’s Disease.

Intranasal introduction of drugs has been a noninvasive method of drug delivery to the brain to overcome blood–brain barrier (BBB) (Ali et al., 2010; Lalani et al., 2014; Yan et al., 2018a,b). Because nasal delivery has a few advantages such as decreased drug delivery to nontarget tissues, averting hepatic first-pass metabolism, drugs such as rasagiline, alginate, tarenflurbil, and piperine are introduced through this route (Haque et al., 2014; Elnaggar et al., 2015; Muntimadugu et al., 2016; Mittal et al., 2016; Yan et al., 2018a,b).

4. Viral vectors

Viral vectors with the capability to infect cells with nucleic acids have also been used as amenable vectors to overcome pathology of several diseases such as PD (Dong et al., 2018). Surprisingly, they offer enhanced transfection efficacy of 80% (Perez-Martinez et al., 2012). A few viral vectors employed for brain delivery include lentivirus, herpes simplex virus (HSV), adenovirus, and adeno-associated virus (AAV) (Fig. 1.1). Despite immunogenicity concerns, AAV exhibited remarkably improved brain delivery and significantly better safety profiles in humans (Mingozzi and High, 2013, Dong et al., 2018). Despite the progress of new viral vectors in the treatment of brain diseases, a few studies involved direct injection of viral vectors into the brain (Natarajan et al., 2017; Tanabe et al., 2017, Dong et al., 2018). Plethora of hitherto employed AAV serotypes exhibited substantial ability to overcome BBB and localize in cells of central nervous system (Zhang et al., 2011; Ahmed et al., 2013; Vagner et al., 2016, Dong et al., 2018). However, a few challenges such as expensive production methods, hurdles in manufacturing, and safety impede their success (Hollo...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Biography
• Acknowledgments
• Chapter 1. Introduction: Parkinson's disease pathology and therapeutics
• Chapter 2. Biomaterials: a boon or a bane in the treatment of Parkinson's disease
• Chapter 3. Blood–brain barrier targeted nanoparticles
• Chapter 4. Natural compounds in the treatment of Parkinson's disease
• Chapter 5. Curcumin: a promising therapeutic in Parkinson's disease treatment
• Chapter 6. Redox nanoparticles: the corner stones in the development of Parkinson's disease therapeutics
• Chapter 7. Liposomal maneuvers against Parkinson's disease
• Chapter 8. Nasal delivery nanoparticles: An insight into novel Parkinson's disease therapeutics
• Chapter 9. α-Synuclein-targeted nanoparticles
• Chapter 10. Pros and cons of Parkinson's disease therapeutics
• Index