Disease Project (Parkinson's Disease)

Parkinson's Disease Name: Institutional affiliation: Course: Date: Introduction Partkinson disease ranks second most neurodegenerative disease after Alzheimer disease. While the disease was mentioned earlier including in text such as “IndianAyurveda” (5000 BC), it is Dr. James Partkinson who first described, accurately, the pathological characteristics of shaking palsy in 1817 and its pattern later called “PD” by Vulpian and Charcot in 1862 (Zeng et al., 2018). Frederick Lewy defined intraneuronal inclusion which define shaking palsy in 1912 and went further to provide a detailed histopathological analysis of the nervous system which further shed light on the understanding of the paralysis agitans. Today, PD is referred to as progressive neurodegenerative disorder and is characterized by severe motor symptoms such as postural imbalance, static tremor, muscle rigidity, and bradykinesia. Technically, α-synuclein is considered the key component of shaking palsy and plays a critical role in PD. Existing epidemiological investigations show that only a small percentage of PD patients are heritable forms, while over 95% of the disease are sporadic form. Accordingly, PD stands as a progressive disease with onset mean age being 55 with incidence rising with age right from about 20/10000 to about 120/100,000 at 70 years (Driver et al., 2009). With the discovery of levodopa (dopamine replacement agent), PD mortality rate has significantly declined, except that use of levodopa triggers an involuntary movement called “dyskinesias” which significantly reduces patients overall quality of life. The mechanism of PD are of key consideration in the paper including molecular mechanism, defective signaling pathways, aeffected Cells, Tissues, and Organs; and current Research and Treatment Approaches. Molecular Mechanisms of Parkinson's Disease PD is considered a multifactorial disease that has both genetic and non-genetic factors playing a role in its development. Notably, the important mechanisms in the development of PD are many and include the failure of protein clearance pathway, aggregation of misfolded proteins, oxidative stress, genetic mutation, mitochondrial damage, accumulation of misfolded protein aggregates, and excitotoxicity (Poewe et al., 2017). Accordingly, proteins remain the main building blocks for the human body. Protein misfolding is a major characteristic of PD and whenever misfolding occurs toxicities such as endoplasmic reticulum (ER) are formed which triggers cellular death as well as photostatic disturbances. Protein often misfold for many reasons including stress induced molecular changes and genetic mutations as triggered with aging or inflammations. Secondly, gene mutation has a role in the development of PD with several studies stating that 5-10% of latest PD cases are linked to genetic factors (Zeng et al., 2018). Ideally, the most common PD related gene is the SNCA (Alpha-Synuclein, DJ-1, LRRK2 (Leucine-Rich Repeat Kinase 2, PARKIN and PINK. First, protein aggregation and misfolding (e.g., alpha-synuclein) are a central pathological features of PD. Often, Alpha-synuclein, which is a presynaptic protein, undergoes a conformational change and ends up forming an iinsoluble aggregates, such as the Lewy bodies and Lewy neurites, within neurons. These aggregates when formed causes disruption in the cellular function and also triggers synaptic transmission impairments, causing major neuronal dysfunction and death. Overall mechanism surrounding the alpha-synuclein aggregation entails an interaction of with other proteins, environmental factors and post-translational modifications. Strategies targeting alpha-synuclein aggregation hold promise for disease-modifying therapies in PD (Maiti, Manna, & Dunbar, 2017). Also, LRRK2 is a multifunctional protein kinase involved in various cellular processes, including vesicle trafficking, autophagy, and inflammation. Dysregulation of LRRK2 activity contributes to neuronal dys...