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New Clues in Understanding the Parkinson's Disease
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Parkinson's disease is a degenerative disorder of CNS (central nervous system). Most people with Parkinson's disease have no specific cause of disease or they have idiopathic disease. However, little percentage of people have genetic factors as cause. Also, there are other factors related to Parkinson's disease development, but we have no proofs for them. The vast majority of patients have both environmental and genetic risk factors. These risk factors are triggers that can lead patient to this neurodegenerative disease. This disease manifests with problems of motor symptoms like uncontrollable trembling of the limbs and non- motor symptoms such as depression and sleeping disorders. Parkinson's disease is the second most common neural disease, after Alzheimer's disease.

Intraneural inclusions are described and named as Lewy bodies. In late 90's, huge discovery happened when scientists found out that Lewy bodies are created when alpha synuclein is aggregated. Since that age, scientist discovered that these alpha synuclein are progressively accumulated within the brain of the patient during the course of disease.
In this disease, alpha synuclein protein aggregates and accumulates within neurons. Some brain regions are affected with this process, and they become more and more affected as disease advances. The whole mechanism of this pathological process is not so clear, but could result from spreading of the abnormal forms of protein along nerve projections between upper and lower regions of the brain.
New experiments with alpha synuclein spreading

German scientists from Bonn have experimented on rats. They figured out the pattern of alpha synuclein protein spreading and they discovered new clues of the mechanism underlying this pathological process. However, the biggest discovery was triggering of production of human alpha synuclein in lower brain and possibility of tracing the spreading toward higher regions of the brain. This experiment and its discoveries could help us to slow down or even stop the development of Parkinson's disease in humans. However, today there is no cure for Parkinson's disease, but there are some symptomatic treatments including dopamine agonists.

Pathology results can support results

Pathology studies from human brains can contribute to research results. These studies show that these alpha synuclein accumulations are formed in lower parts of the brain. Typical place where these accumulations occur is medulla oblongata. After examination on subsequent stages of Parkinson's disease, alpha synuclein aggregations are found on higher levels of human brain such as cortical areas and midbrain.

It seems that spreading follows a typical pattern. This pattern is based on anatomical connections between various regions of the brain. Because of this assumption, it was hypothesized that abnormal forms of alpha synuclein or alpha synuclein itself can migrate from one brain region to another, in most cases from lower part to more rostral, upper part. Until now, it was not possible to target medulla oblongata to reproduce this spreading in the lab. However, there are more unrevealed things, and the biggest question is in what conditions the inter- neural passage of protein or its aggregates could be triggered. This question could be answered soon, because researchers have developed a new paradigm which could enable investigations and experiments on important and fundamental issues.

Start location of Parkinson's disease

The researchers' concept was based on creating alpha synuclein spreading in rats. Transfer of blueprint of human form of alpha synuclein into the rat brain was required in order to fulfill this concept. Specially engineered viral particles were used in transport of blueprint. After that procedure, scientists have injected it into nerve fibers in animals neck. Genetic code for the protein migrated along nerve fibers into the medulla oblongata. In rats medulla oblongata, neurons began producing huge quantities of human alpha synuclein.

Results show that scientists have solid reasons to believe that primary site of early disease development is exactly medulla oblongata. There were many reasons why scientists wanted to place alpha synuclein exactly in this part of brain. However, concept was not so simple, because medulla oblongata is not so easy to reach. They had to use vagus nerve by injecting alpha synuclein in it. This nerve was ideal because it stretches from abdomen to medulla oblongata. Because of this property, this nerve was very good solution for researchers.

Way of alpha synuclein spreading in experimental researches on rats?


Production and localization of human alpha synuclein rats brains was carefully observed by scientists during the four and a half months. As it was predicted, production and localization exogenous protein was in medulla oblongata near the connection with vagus nerve. After two months, scientist have noticed that alpha synuclein was located more distant than in the beginning. Caudo- rostral spreading involved transport of specific protein via specific nerve tract.

Possible trigger for alpha synuclein propagation

Results of the previous researches have shown that possible trigger for protein transmission is overproduction of alpha synuclein in specific brain regions. Also, overproduction of alpha synuclein is accompanied with variety of conditions such as neuronal injury, aging or genetic polymorphism. These conditions could promote development of Parkinson's disease. Because of that, many researchers results suggest a link between spreading of the protein and its pathological accumulation, disease risk factors and enhanced levels of human alpha synuclein.

The importance of insight into the early stages of Parkinson's disease

The insight into the early stages of Parkinson's disease is very important. The new model could hide the events that could possibly occur in the early stages of alpha synuclein pathology, especially when behavioral manifestations in rats and clinical manifestations in human are lacking. Because of that, it will become irreplaceable tool of investigation for mechanisms of disease pathogenesis. The biggest importance of these mechanisms is that they could be targeted for therapeutic intervention. If scientist find the way to intervene early, that would gain us a greater ability to prevent spreading of pathology or even stopping progression of disease.
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New Clues in Understanding the Parkinson's Disease - by sale0303 - 05-26-2013, 11:59 PM
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New Clues in Understanding the Parkinson's Disease00