The Parkinson's Disease

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

HD, in contrast, is not a condition offset by the environment, as PD is thought to be. It is indeed a condition due to cell death in the brain (basal ganglia) but is caused by an abnormal gene that codes for a mutant protein called huntingtin. Huntingtin, thus, interferes with normal brain cell functions by causing a depletion in neural cellular energy and neural death (12)(9).

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

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).

Primary prevention -- using methods to prevent a disease before it begins -- requires an understanding of the disease’s cause. Most cases of PD are idiopathic; these result from an interaction between genetic factors and the environment (Heath, 2011). Five to ten percent of PD cases are due to inherited genetic mutations (Gillies et al., 2014; Heath, 2011). The largest risk factor for developing PD is increased age (Stacy et al., 2009). PD has a

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.

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.

PD is increasingly recognized as an extensive multi-system disease with widespread neurological impairment, affecting a variety of brain regions not directly involved in motor control. The extranigral pathology includes the olfactory bulb, the dorsal motor nucleus of the glossopharyngeal and vagal nerves, the intermediate reticular zone, subnuclei of the reticular formation and the raphe system, the locus coeruleus (LC), regions of the basal forebrain, many subnuclei of the thalamus and amygdala, and, in severe cases, the neocortex [64-67]. In 2003, Heiko Braak and colleagues [68] traced the course of the pathology in incidental PD cases and developed a staging procedure based on the location of α-synuclein-containing inclusion bodies, also

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized mainly by physical and psychological disabilities. This disorder was named after James Parkinson, an English physician who first described it as shaking palsy in 1817 (Goetz, Factr, and Weiner, 2002). Jean- Martin Charcot, who was a French neurologist, then progressed and further refined the description of the disease and identified other clinical features of PD (Goetz, Factr, and Weiner, 2002). PD involves the loss of cells that produce the neurotransmitter dopamine in a part of the brain stem called the substansia nigra, which results in several signs and symptoms (Byrd, Marks, and Starr, 2000). It is manifested clinically by tremor,

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

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

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

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

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

These genes have become a central theme in PD pathogenesis and may hold the key to future novel therapeutics. Using Drosophila as the study model, the Guo lab have shown PINK1 mutants exhibit vacuolations in mitochondria and aggregations of PINK1 proteins to nebenkerns, a large spherical structure composed of two intertwined mitochondria essential for proper spermatogenesis in Drosophila (Deng, Dodson et al. 2008). The Guo lab have also shown null PINK1 flies exhibit phenotypes similar to that of sporadic PD: male sterility, held-up wings due to muscle defects, features of apoptosis, reduced ATP/mtDNA, cristae fragmentation, and vacuolations of the mitochondria. From epistatic studies, the over expression of PARKIN in PINK1 mutant models caused rescue of mitochondrial defects associated to PINK1 mutants indicating the two genes are utilized in a common pathway. The reverse rescue, over expression of PINK1 to PARKIN mutants, did not show any improvement in the mutant phenotype and is suggestive that PINK1 is upstream from PARKIN (Dodson and Guo 2007). The Guo lab has also shown that the expression of human PINK1 in Drosophila PINK1 mutants restored mitochondrial defects