The Parkinson's Disease

The cause of Parkinson disease, defined by Robert Hauser, who is an author of Medscape, is still unclear. Studies state that there is a combination of environmental and genetic factors for this particular disease. Approximately 10% of cases are currently genetic causes of Parkinson disease. Environmental risk factors such as use of pesticides, living in a rural environment, consumption of well water, exposure to herbicides, and proximity to industrial plants or quarries are commonly associated with the development of Parkinson disease (Hauser, 2016). In addition, according to Hauser, “genetic factors in Parkinson disease appear to be very important when the disease begins at or before age 50 years. In a study of 193 twins, overall concordance for MZ and DZ pairs was similar, but in 16 pairs of twins, in whom Parkinson disease was diagnosed at or before age 50 years, all 4 MZ pairs, but only 2 of 12 DZ pairs, was concordant.The identification of a few families with familial Parkinson disease sparked further interest in the genetics of the disease.

Identified as LRRK2, this gene mutation only accounts for one to two percent of all cases of Parkinson’s disease. (Michael J. Fox Foundation)

Some experts believe this disease is related to the inhalation of pesticides, while others believe it results from the inhalation of chemical elements such as copper, lead, or manganese. It has been linked to heredity. It is believed that 15% of those diagnosed with the disease have a family history of the mutated gene. Scientists believe there are two types of carriers for this gene that determines a diagnosis of Parkinson’s Disease. The first type of carrier guarantees a diagnosis, whereas the second type of carrier only increases the chance of being diagnosed. This theory has yet to be

In Parkinson's Disease and Huntington's disease the nigra-striatum neural communication assemblage is severely hampered. PD results from a depletion in the amount of dopamine produced by the brain. At the onset of the disease, dopamine-secreting cells of the substania nigra, either because of genetic factors or environmental toxins, experience mass cell death. Thus, the nigra cells are unable to form synapses through which they secrete and relay dopamine to the striatum in a neural circuit within the basal ganglia (18).

It is thought that PDK is caused by mutations of the genes on chromosome 16 or chromosome 4. The disease process begins with the appearance of cysts, which grow out of the nephrons of the kidneys.

Unfortunately by the time that PD is first diagnosed, 60% to 70% of the neurons in the SN responsible for dopamine have degenerated and the striatal dopamine content is reduced by 80% (Adler, 2011) and

It has been well established that α- synuclein plays a role in the pathogenesis of PD (Spillantini MG et al., 1997; Wakabayashi et al 2007; Polymeropoulos MH et al., 1997; Singelton et al., 2003; Maries E et al., 2003). α-synuclein accumulates within the SN neurons, where it is trapped inside granules of pigments during the synthesis of neuromelanin much before there is evidence that neuromelanin is depleted in PD (Fasano M et al, 2003; Ikemura M et al, 2008; Michell AW et al., 2005). In PD, the peripheral nervous system (PNS) is also affected which is demonstrated by the fact that α-synuclein is also found in aggregates throughout the nervous system, including, enteric nervous system, sympathetic ganglia, submandibular gland, cardiac and pelvic plexuses, the skin and adrenal medulla (Shishido et al, 2010; Wakabayashi et al., 2010). It has been shown that α-synuclein immunoreactivity is increased in cutaneous peripheral nerves of PD when compared to those with other neurodegenerative disorders (Paisan Ruiz et al., 2009).

PD affects 50 percent of more men than women but scientist till this day don’t understand why it hits men more. One huge risk about PD is aging. It is sad that the average age of someone to get PD is 60 years and as they get older the disease starts to significantly rises. It is rare for people younger that can get it. Studies show that about 5 to 10 percent of people can get PD before

The onset for Parkinson’s disease is progressive and increases as age increases. It commonly develops in patients around the 50 years of age and the prevalence is 4% to 5% in patients older than 85 years of age. Kluwer (2015) Based on the etiology, Parkinson’s disease is considered to be a nonhereditary disorder, however there is evidence that the environmental factors may contribute to some etiologic associations. The associated environmental risk factors include expo¬sure to well water, pesticides, herbicides, industrial chemicals, wood pulp mills, fanning, and rural resi¬dence. Moreover, there is evidence that genetics may play a major factor in Parkinson’s disease. According to Nolden, et al.’s (2014), a gene mutation called alpha-synuclein

Scientists generally agree that most cases of Parkinson’s disease result from some combination of nature and nurture the interaction between a people’s underlying genetic make-up and his or her life activities and environmental exposures. A simple way to describe this is that “genetics loads the gun and environment pulls the trigger.” In this formulation, “environment” has a very broad meaning that is, it refers to any and all possible causes other than those that are genetic in origin. The interactions between genes and environment can be quite complex. Some environmental exposures may lower the risk of PD, while others may increase it. Similarly, some people have inherited a genetic makeup that makes them more or less susceptible to the effects of toxicants, or poisonous agents, than others. The effect of a combined exposure can be greater or lower than a single exposure. All of this means that the particular combination of factors leading to PD is likely to be unique for each person. These combinations, in different ways, may trigger a common series of biological changes that will ultimately lead to the disease. Scientists are beginning to tease apart the non-genetic factors that influence PD risk. In particular, epidemiologists are working to identify differences in the experiences of people who develop PD, compared to those who do not. But identifying these risk factors can be difficult.

Over a 2-year span 260 participants having PD were examined. To be selected for this

One mechanism is the aggregation of the misfolded alpha-synuclein proteins, causing the death of the dopaminergic neurons in the brain tissue (Dauer and Przedborski, 2003; Sultana et al. 2011). A second proposed mechanism is mitochondrial dysfunction, causing oxidative stress on the neurons promoting the activation of ROS (reactive oxygen spcies) thus causing apoptosis of the neuronal cells (Dauer and Przedborski, 2003; Zhang et al. 2012). Other mechanisms and links between these two proposed models have been suggested but further research is necessary to determine the direct pathways of neuronal death in PD. The root to the biochemical alteration in the dopaminergic neurons is a mixture of environmental effects and exposures as well as genetic factors. The genetic inheritance of Parkinson’s disease only affects approximately 10% of persons with PD (Shahaduzzaman et al. 2013) and is usually inherited from a direct relative (Elbaz and Tranchant, 2007). Environmental factors such as exposure to pesticides, traumatic brain injury, and age are believed to contribute to the development of PD and pose a possible threat to mutation of the genes involved in PD (Hassan et al. 2015). The multifactor of the involvement of environmental factors as well as genetic factors are believed to attribute for the majority of cases of

Parkinson’s disease (PD) is the most frequent movement disorder and the second most common neurodegenerative disease (Bueler 2009). Over 1% of the entire population over the age of 60, and up to 5% of age 80, is affected by PD (Wood-Kaczmar, Gandhi et al. 2006). The pathogenesis of PD remains unclear, but can be categorized as sporadic, being the most common form, and Mendelian, which accounts for 5-10% of all PD cases (Guo 2008). The studies of Mendelian onset of PD have lead to the identification of five genes being linked to this neurodegenerative disease (Guo 2008). α-Synuclein (SNCA) and Leucine-rich repeat kinase 2 (LRRK2) mediate autosomal dominant forms of PD. PTEN-induced putative kinase 1 (PINK1),

Due to years of research for Parkinson’s, a current theory known as Braak’s Hypothesis, discusses that the beginning signs for the disease is found in the nervous system, medulla, and olfactory bulb. According to Braak and his colleagues they have found that, “The Braak hypothesis not only proposes that lower brainstem pathology is a necessary pre-condition for the occurrence of PD, but also that it is sufficient. In other words, there is such a compelling liklihood that Stage 1 or Stage 2 synuclein pathology will evolve to Stages 3 or 4, and, more importantly, evolve to manifest clinical parkinsonism that this pathology can be considered to represent “early PD”, as has been claimed. (NCBI)” This hypothesis

Overall Goal: Determine challenges in developing a clinically meaningful model of PD heterogeneity, subtypes, a progression model and the high-level method for a roadmap around these challenges