Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disorder in which a progressive loss of the dopaminergic neurons occurs. The loss of the neurons is most prominent in the substantia nigra region of the brain. The prevalence of PD is much greater among the older patients suggesting the risk of PD increases with the increase of age. The exact cause of the neurodegeneration in PD is not known. In this chapter, the authors introduce PD, demonstrate its history, pathogenesis, neurobiology, sign and symptoms, diagnosis, and pharmacotherapy.

Amyloid Beta

Alzheimer's disease (AD), exhibiting accumulation of amyloid beta (Aβ) peptide as a foremost protagonist, is one of the top five causes of deaths. It is a neurodegenerative disorder (ND) that causes a progressive decline in memory and cognitive abilities. It is characterized by deposition of Aβ plaques and neurofibrillary tangles (NFTs) in the neurons, which in turn causes a decline in the brain acetylcholine levels. Aβ hypothesis is the most accepted hypothesis pertaining to the pathogenesis of AD. Amyloid Precursor Protein (APP) is constitutively present in brain and it is cleaved by three proteolytic enzymes (i.e., alpha, beta, and gamma secretases). Beta and gamma secretases cleave APP to form Aβ. Ubiquitin Proteasome System (UPS) is involved in the clearing of Aβ plaques. AD also involves impairment in UPS. The novel disease-modifying approaches involve inhibition of beta and gamma secretases. A number of clinical trials are going on worldwide with moieties targeting beta and gamma secretases. This chapter deals with an overview of APP and its enzymatic cleavage leading to AD.

Neurodegenerative Disorders

Neurodegenerative diseases (NDs) are characterized by specific dysfunction and damage of neurons related to pathologically changed proteins that deposit in the patient brain but also in peripheral organs. These proteins can be used for therapy or used as biomarkers. Except for a plethora of alterations revealed for dissimilar neurodegeneration-related proteins, amyloid-β, prion protein, TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa), tau and α-synuclein, or fused in sarcoma protein (FUS), molecular classification of NDs depend on the full morphological assessment of protein deposits, their spreading in the brain, and their correspondence to clinical signs with specific genetic modifications. The current chapter represents the etiology of neurodegeneration, classification of NDs, concentrating on the maximum applicable biochemical and anatomical characteristics and most imperative NDs.

Alternation of Mitochondrial and Golgi Apparatus in Neurodegenerative Disorders

Neurodegenerative disorders (NDs) are characterized by dysfunction and loss of neurons associated with altered proteins that accumulate in the human brain and peripheral organs. Mitochondrial and Golgi apparatus (GA) dysfunctions are supposed to be responsible for various NDs. Damaged mitochondria do not produce sufficient adenosine triphosphate (ATP) and produce reactive oxygen species (ROS) and pro-apoptotic factors. Mitochondrial dysfunctions may be caused by various factors such as environmental causes, mutations in both nuclear or mitochondrial deoxyribonucleic acid (DNA), that code many mitochondrial components. Three factors that are mainly responsible for the morphological changes in GA are certain pathological conditions, drugs, and over expression of Golgi associated proteins. In this chapter, common aspects of mitochondrial and GA dysfunction concerned about NDs are summarized and described for Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD).

Mitochondrial Dysfunction in Aging and Neurodegeneration

Mitochondria are a dynamic organelle of the cell involved in the various biological processes. Mitochondria are the site of the adenosine triphosphate (ATP) production, electron transport chain (ETC), oxidation of fatty acids, tricarboxylic acid (TCA), and cellular apoptosis. Besides these, mitochondria are the site of production of reactive oxygen species (ROS), which further disrupts the normal functioning of this organelle also making mitochondria itself as an important target of oxidative stress. Thus, mitochondria serve as an important target in the process of neurodegeneration. In the present chapter, the authors describe mitochondria and its functioning, dynamics, and the mitochondrial dysfunction in aging and neurodegenerative disorders (NDs).

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder (ND) that primarily comprises the neurons responsible for controlling voluntary muscle movement. The unique neuropathologic findings include anterior horn cell degeneration producing muscle atrophy or amyotrophy, degeneration, and sclerosis of the corticospinal tracts. It is a common neuromuscular disease worldwide and has been identified in people of all races. There seems to be neither identified risk factors nor family history associated with most of the documented ALS cases. There exists no treatment for ALS that can prevent neither its progression nor reverse its development. However, there are treatments available that can help control symptoms, prevent unnecessary complications, and make living with the disease easier. This chapter extensively discusses this neurodegenerative disorder based on the currently available knowledge on the condition.

Neurodegenerative Disorders Progression

Neurodegenerative disorders (NDs) are a diverse group of disorders characterized by selective and progressive loss of neural systems that cause dysfunction of the central nervous system (CNS). The examples of NDs include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD). The aggregated proteins block or disrupt the normal proteosomal turnover, autophagy, and become abnormally modified with time, generating toxicity via pathways thereby resulting in neurodegeneration and neuron death. The chapter highlights the understanding in the areas of AD, PD, HD as illustrative of major research so as to define the key factors and events in the improvement of NDs. It defines the physiological functioning of neural transmission (presynaptic, postsynaptic activity) at neural signaling pathway, then the dynamics of neuronal dysfunctioning and its molecular mechanism. Further, it also discusses the progression from synaptic dysfunction to transmission failure followed by NDs.

The Aging Brain

Neurodegeneration is the progressive and gradual dysfunction and loss of axons in the central nervous system. It is the main pathological characteristic of chronic and acute neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). The usual aspects of pathogenesis of disease can be abridged with regards to the downstream implications of uncontrollable protein oligomerization and aggregation from postmitotic cells. The brain structure constantly changes in normal aging without any dysfunction accompanying the structural changes in brain. The decline in cognitive capabilities, for example, processing speed, memory, and functions related to decision making are the sign of healthy aging. The reduction in brain volume in healthy aging is possibly related to neuronal loss at some marginal extent. The following chapter discusses the structural and functional alterations in the brain in ageing and neurodegeneration.

Lewy Body Disease

Fritz Heinrich Lewy described the intracytoplasmic inclusions found in the neurons for the very first time. In 1919 these inclusions were termed as “LBs” by Tretiakoff. LBs were found in the brain of the patients suffering from Lewy body disease (LBD). LBD is characterized by the presence of Parkinsonian symptoms in the earlier stages and dementia in the later stages of the disease. LBs were classified on the basis of the region of the brain in which they are distributed and so is the case of the LBD means the type of the LBD depends on the anatomical areas of the brain involved. LBD is not a single disorder. It is a spectrum of disorders. This chapter addresses the entire profile of LBs, types, composition, formation, and various LB pathologies as well as diagnostic criteria and pharmacotherapy.

Zinc and Neurodegenerative Disorders

Zinc (Zn) is an essential trace element that is abundantly present in humans. Despite its importance in normal brain functions, alterations in zinc homeostasis cause various neurological pathologies such as dementia, Parkinson's disease, Prion's disease, etc. A growing body of evidence has shown that zinc might play a dual role: in which both zinc depletion and excess zinc cause severe damage and hence neurotoxicity develops. Homeostatic controls are put in place to avoid the accumulation of excess zinc or its deficiency. This cellular zinc homeostasis results from the actions of a coordinated regulation effected by different proteins involved in the uptake, excretion, and intracellular storage or trafficking of zinc. Further investigation has also shown the role of endogenous carnosine (beta-alanyl-L-histidine) in binding excess zinc. Hence, it has the ability to prevent neurotoxicity. Also, the role of a zinc-rich diet cannot be overemphasized. The authors of the chapter, however, provide an insight into the link between zinc homeostasis and neurodegenerative disorders (NDs).