Faithin Omaha eBook Collection

Download or read book Analysis of Genetic and Environmental Factors in Neurodegenerative Disease written by Marleshia Dorcell Hall and published by . This book was released on 2016 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: The incidence of neurodegenerative diseases including Parkinson's, Alzheimer's, and Huntington's disease is ever-increasing. Therefore, it is essential that we understand the mechanisms behind the pathology of these disorders. Extensive study has been conducted on the factors that play a role in these disorders. Through these studies, several pathways have been elucidated that further enlighten our understanding of these pathologies. However, many studies have been conducted on model systems that do not fully recapitulate all of the pathological hallmarks of these diseases. Additionally, a greater understanding into the interplay between multiple pathways has been lacking. Previously, we established a Drosophila model for Parkinson's disease that demonstrates that both genetic and environmental factors play a role in the susceptibility and resistance of the organism to neurodegenerative disease. The herbicide paraquat leads to degeneration of dopamine neurons and reduced mobility as is seen in Parkinson's patients. Using this model, we determined that an integration of the inflammatory and hypoxia pathways ensues whereby ingestion of paraquat induces the production of nitric oxide synthase (NOS) that is associated with hyper-branching of the trachea; this also occurs in adult Drosophila brains. Additionally, we have investigated the role of von Hippel Lindau (VHL), an E3 ubiquitin ligase that regulates the hypoxia response, in sensitivity to paraquat, induction of the inflammatory pathway, and neurodegeneration. We have found that loss of VHL along with exposure to paraquat leads to exacerbated survival truncation and movement abnormalities. Furthermore, Catsup protein levels (a negative regulator of dopamine biosynthesis) are altered in these mutants demonstrating a putative role for VHL in Catsup regulation. Here, we also show that a metabolite from the common soil bacteria Streptomyces venezuelae leads to decreased survival and loss of dopamine neurons and induction of NOS. Additionally, Îł-synuclein, a gene implicated in familial Parkinson's disease was studied to determine susceptibility to this bacterial metabolite. We found that expression of Îł-synuclein in flies leads to increased sensitivity and loss of dopamine neurons due to the toxic bacterial metabolite. Taken together, this work provides a mechanism behind the pathology of neurodegenerative diseases and signifies that both genetic and environmental factors play a role in the development and progression of these diseases. It also demonstrates that a dynamic interplay of pathways exists and provides avenues by which future therapeutics may be developed.