Causes Of Parkinson's Disease

Parkinson disease (PD) is one of the most common neurologic disorders. and it affects approximately 1% of individuals older than 60 years old. Parkinson’s disease is a condition that progresses slowly by treatment. In addition, loss of pigmented dopaminergic neurons of the substantianigra pars compacta and the presence of Lewy bodies and Lewyneurites are the two major neuropathologic findings in Parkinson disease (Hauser, 2016).

James Parkinson first described the disease named after him as a motor dysfunction through an essay on “shaking palsy” in the early nineteenth century, with Friedrich Lewy a century later describing atypical masses of protein (now known as Lewy bodies) within cell cytoplasm’s in the brainstems of those displaying symptoms of Parkinson’s disease including those with dementia. Because of the distinct similarities, there has been professional discussion that Parkinson’s disease, Parkinson’s with dementia, and dementia with Lewy bodies be grouped as one: Lewy Body Disease (Auning, E., A., & Aarsland, D., 2012, p. 233). Dementia associated with Parkinson’s is frequent, with the occurrence assessed. Those with Parkinson’s disease with dementia represent 5% of all people who have dementia, and of

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most widespread age-related neurodegenerative diseases. Both diseases impact a considerable number of people, where AD occurs in around 10 percent of the population greater than the age of 65 while PD occurs in roughly 1 percent of the population above the age of 65. AD is considered to be the most widespread cause of dementia, characterised by the progressive memory and cognitive deficits which impair ones day to day activities. The pathological hallmark of AD comprises of extracellular accumulation of senile plaques consisting of mainly amyloid-beta (Aβ) peptides, along with neurofibrillary tangles which are composed of the phosphorylated tau protein, located in the hippocampus and cortex. Conversely, PD is considered to be the most widespread movement disorder that is characterised by symptoms such as rigidity slow movements, resting tremor and other instabilities. The extreme loss of dopaminergic neurones in the substantia nigra is what defines PD, as the loss of this nerve cell can be linked to Lewy bodies containing aggregates of a soluble protein called α-synuclein.

Parkinson's disease (PD) is an adult-onset neurodegenerative disorder, concomitant with neuronal loss predominantly in the substantia nigra pars compacta (SNpc) and inclusions comprising of the synaptic protein, α-synuclein (α-syn). Recent developments have advanced our understanding on the multitude of inter-mingled deleterious factors contributing to PD neuropathological aetiologies. These encompass “cell autonomous” processes, for instance, autophagy, and mitochondrial dysfunction, and “non-cell autonomous” processes, which embrace trans-synaptic transmission of abnormal proteins and neuro-inflammation (Foltynie and Kahan; 2012). Although the “prion-like” nature of pathological α-syn is a theme of intense research

The PARK7 gene provides instructions for making the DJ-1 protein. This protein is found in many tissues and organs, including the brain. Studies indicate that the DJ-1 protein has several functions, however it is not fully understood how generic changes cause Parkinson’s disease or even understand it’s risks. One of the protein's functions may be to protect cells, particularly brain cells, from oxidative stress. Oxidative stress reflects an imbalance between the generation reactive oxygen species and a biological system’s ability to readily detoxify the reactive species. It occurs when unstable molecules called free radicals accumulate at levels that can damage or kill cells. Many radicals are unstable and highly reactive. They can neither donate or accept an electron. Additionally the DJ-1 protein may assist in delivering selected proteins to proteasomes, which are structures within cells that break down unneeded

Aside from genetics there also can be environmental toxins that may increase the risk of Parkinson’s, but this isn’t until later down the road. The risk of getting the disease from toxins is pretty small, and isn’t a main

The National Parkinson Foundation states “When approximately 60 to 80% of the dopamine-producing cells are damaged, and do not produce enough dopamine, the motor symptoms of Parkinson's disease appear.”(National Parkinson Foundation) Scientist still do not know for sure why the cells deteriorate. There is also a lack of a chemical called norepinephrine, which is produced by nerve endings that patients have lost. Norepinephrine is a chemical that is very similar to dopamine it sends messages through the nervous system, and is the main chemical used for transmitting messages. “Lewy bodies are unusual deposits or clumps of the brain protein alpha-synuclein, along with other proteins, which are seen upon microscopic examination of the brain.”(Heyn) The purpose and influence of Lewy Bodies is still unknown to scientist. Scientist believe that the cause is influenced by genetics and environment. There have been 5 different genes that are linked to the disease. SNCA, PARK2, PARK7, and PINK1 are 4 genes that are related to Parkinson’s, and these 4 are known to cause early-onset when there is a mutation in any of these genes. LRRK2 is the 5th gene that causes late-onset Parkinson’s.

Parkinson’s disease is affected by the degeneration of dopaminergic neurons which is responsible to produce dopamine. Dopaminergic neurons have their cell bodies in substantia nigra pars compacta (SNpc) in basal ganglia (O’Sullivan and Schmitz, 2007). Basal ganglia are a collection of interconnected gray matter nuclear masses deep within the brain”. These gray matter masses are caudate, putamen, globus pallidus, subthalamic nucleus and the substantia nigra. Basal ganglia receive its input through striatum (O’Sullivan and Schmitz, 2007).

Scientists are clueless why lewy bodies are formed and what is their role in Parkinson’s. But clumps of lewy bodies’ results in brain degeneration, causing problems with motor coordination in people affected with Parkinson’s disease.

Parkinson 's disease (PD) is the second world 's major neurological disease (Laut & Breteler, 2006) affecting 6 million people globally (Schapira, 1999). PD is a progressive and long term disorder of the central nervous system (CNS) activity with the following traits including bradykinesia, rigorousness, involuntary muscular contraction and unstable postural alignment (O ' Sullivan & Schmitz, 2007). Basal ganglia are located in the CNS have large nerve fibers and neurotransmitters for controlling all types of movement (Ciccone, 2016). The main neurotransmitters of the basal ganglia including substantia nigra which produces dopamine and dopamine normalize the neurons of the basal ganglia (Goodman & Fuller, 2015). The neural activity in PD is the imbalance of the dopamine pathways that conjoined with the substantia nigra to the striatum (Agid, 1991). Michell, (2004); Lang & Obeso (2004) identified that dopamine depletion is also due to an increase degeneration of the neurons of the brain structure with a consequence of changes in conduction to the other neural pathways. Also, there are non- living substance unable to carry out any metabolic benefits ad was unprotected by membranes called Lewy bodies (Michell, 2004; Lang et al., 2004).

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. Parkinson disease Foundation has estimated that around 1 million people suffer from the disease in USA. Deterioration of dopamine producing neurons in the brain causes PD. Dopamine is an essential neurotransmitter that controls both smooth and coordinated muscle function [1].

Parkinson's disesae is an interminable, dynamic neurodegenerative issue with expanded predominance in the maturing populace.

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,

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the classical motor symptoms: resting tremor, bradykinesia, akinesia, rigidity and postural instability. Although the complete PD pathogenesis is not well understood, we have gained a better understanding of its etiology, pathology, and molecular mechanisms, thanks to the use of animal models. Importantly, none of the current available models is able to fully recapitulate PD symptoms and pathology. Each model is based on the production of one or few pathological processes of PD, which are either artificially induced in a way that is seldom relevant to the disease (like toxin models), or that produces only a small part of the pathology (like genetic models).

Prominent pathological facet of Parkinson’s Disease(PD) is the accumulation of intracytoplasmic lewy bodies caused by dominant mutations in ⍺-synuclein gene (SNCA). Recent studies suggest the role of toxic ⍺-synuclein oligomers in impairing several important cellular activities such as redox stability, mitochondrial functions, proteasomal and lysosomal degradation. Previous studies using a mouse model overexpressing A53T-SNCA by Mahalakshmi et al in Prof. Jochen Roeper’s lab, has found that under in-vivo conditions there is a Sustantia Nigra (SN) selective increase in action potential