Browsing by Subject "Parkinson's Disease"

Now showing 1 - 5 of 5
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    C9orf72 Intermediate Repeats are Associated with Corticobasal Degeneration, Increased C9orf72 Expression and Disruption of Autophagy
    (Springer, 2019-11) Cali, Christopher P.; Patino, Maribel; Tai, Yee Kit; Ho, Wan Yun; McLean, Catriona A.; Morris, Christopher M.; Seeley, William W.; Miller, Bruce L.; Gaig, Carles; Vonsattel, Jean Paul G.; White, Charles L.; Roeber, Sigrun; Kretzschmar, Hans; Troncoso, Juan C.; Troakes, Claire; Gearing, Marla; Ghetti, Bernardino; Van Deerlin, Vivianna M.; Lee, Virginia M.-Y.; Trojanowski, John Q.; Mok, Kin Y.; Ling, Helen; Dickson, Dennis W.; Schellenberg, Gerard D.; Ling, Shuo-Chien; Lee, Edward B.; Pathology and Laboratory Medicine, School of Medicine
    Microsatellite repeat expansion disease loci can exhibit pleiotropic clinical and biological effects depending on repeat length. Large expansions in C9orf72 (100s-1000s of units) are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). However, whether intermediate expansions also contribute to neurodegenerative disease is not well understood. Several studies have identified intermediate repeats in Parkinson’s disease patients, but the association was not found in autopsy confirmed cases. We hypothesized that intermediate C9orf72 repeats are a genetic risk factor for corticobasal degeneration (CBD), a neurodegenerative disease that can be clinically similar to Parkinson’s but has distinct tau protein pathology. Indeed, intermediate C9orf72 repeats were significantly enriched in autopsy-proven CBD (n=354 cases, odds ratio=3.59, p-value=0.00024). While large C9orf72 repeat expansions are known to decrease C9orf72 expression, intermediate C9orf72 repeats result in increased C9orf72 expression in human brain tissue and CRISPR/cas9 knockin iPSC derived neural progenitor cells. In contrast to cases of FTD/ALS with large C9orf72 expansions, CBD with intermediate C9orf72 repeats was not associated with pathologic RNA foci or dipeptide repeat protein aggregates. Knock-in cells with intermediate repeats exhibit numerous changes in gene expression pathways relating to vesicle trafficking and autophagy. Additionally, overexpression of C9orf72 without the repeat expansion leads to defects in autophagy under nutrient starvation conditions. These results raise the possibility that therapeutic strategies to reduce C9orf72 expression may be beneficial for the treatment of CBD.
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    Caregiver Burnout Prevention at a Midwest Parkinson's Foundation
    (2024) Goyke, Madison; Bednarski, Julie; Department of Occupational Therapy, School of Health and Human Sciences; Williams, Kim
    Parkinson’s Disease is a rapidly growing neurological condition that can affect participation in everyday activities. As more individuals become diagnosed with Parkinson’s Disease, the number of those caring for people with Parkinson’s Disease also increases. Caregivers can become susceptible to caregiver burnout, which is a stress that accumulates over time, produces a negative outlook on caregiving, and affects many areas of one’s life. Literature suggests that key areas to caregiver burnout prevention are daily care hours, education on disease, social support, and mindfulness. Through a needs assessment of a midwest Parkinson’s organization, a gap was identified between where the organization wanted to be with caregiver burnout prevention and where it was. The goal of this capstone project was to equip the organization with caregiver burnout prevention resources and strategies to promote caregiver health, well-being, and quality of life. Based on the needs assessment, two educational sessions were created and delivered to participants at three caregiver support groups over the topics of mindfulness, medication management, Lee Silverman Voice Treatment (LSVT), and respite. Program outcomes were measured via pre- and post- surveys, and this data was analyzed through independent t-tests. There was a statistically significant difference with a large effect size for mindfulness, medication management, and respite educational sessions. Outcomes suggested that caregiver confidence and satisfaction in applying burnout prevention strategies greatly increased following the educational sessions.
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    Cell model of DJ-1-associated Parkinson’s Disease
    (2017-10-31) Madison, Mackenzie; Hoang, Quyen; Wang, Mu; Hudmon, Andy
    Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of motor function resulting from dopaminergic neuronal death in the substantia nigra pars compacta leading to subsequent decreased striatal dopamine levels. The majority of PD cases are diagnosed as sporadic in nature, however 10% - 15% of patients show a positive family history of the disease. While many genes have been found to be implicated in the familial form of PD, early-onset autosomal recessive PD has been associated with mutations in PARK7, a gene which codes for the protein DJ-1. While there are many proposed roles of DJ-1 across numerous systems, the function of DJ-1 in relation to the development and progression of PD remains largely unclear. A first step towards determining this function is the creation of biologically relevant cell models of PD. The goal of this work was to design a representative cell model of DJ-1-associated PD in order to further study DJ-1 with the intention of elucidating its relevant function in relation of PD pathogenesis.
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    The Effectiveness of Dance Intervention for Parkinson's Disease
    (2021-05-06) Messer, Kyle; Albright, Megan; Department of Occupational Therapy, School of Health and Human Sciences; Williams, Kim
    Fear of falling and increased fall risk is a common issue for individuals with Parkinson’s Disease (PD). Secondary to balance and coordination complications experienced these individuals can experience extreme difficulty navigating their environment because of compromised mobility. This difficulty can manifest, causing mobility issues, insecurity with functional mobility, and transitioning from one position to another. The resulting effects of PD can drastically influence the quality of life in which individuals with PD experience. The impact can present in fear of transferring from seated to standing positions, inability in completing daily self-care tasks, inability to participate in activities which bring an individual enjoyment, and result in significant fatigue levels experienced. The purpose of this doctoral capstone experience is to introduce dance as a fun and interactive exercise-based intervention. Ideally, introducing a Samba dance style to the participants of the study will decrease the risk/frequency of falls among participants, improve engagement in Activities of Daily Living (ADL)/ Instrumental Activities of Daily living (IADL) and improve quality of life. During the study, participants engaged in one weekly Samba dance intervention accompanied by a warm-up and stretch routine to address issues. Four separate subjective assessments were implemented addressing independence with ADL/IADLs, a fall risk/mobility measure, an assessment addressing fatigue levels experienced, and a measurement to see the strain placed on caregivers. The results of the study are inconclusive and have several statistical variations among the four participants which completed both -pre and -post-assessments. The doctoral capstone student hypothesized that with objective measures implemented, increased frequency of the intervention, and a larger sample size a similar, future study may provide positive results when addressing improvements in independence with ADL/IADL performance, improved mobility/decrease in fall risk, and improved overall quality of life.
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    The role of SMF 1, SMF-2, SMF-3 in metal-induced whole animal vulnerability and dopamine neuron degeneration in Caenorhabditis elegans
    (2012-12-04) LeVora, Jennifer K.; Nass, Richard M.; Nicol, Grant D.; Hingtgen, Cynthia M., 1966-
    The etiology of many neurodegenerative diseases is unknown, but a number of studies indicate that a combination of both genetic and environmental factors contribute to the progression of disease. Exposure to environmental metals, such as Mn2+, Fe2+, Cu2+, and Al3+, has been shown to increase cell death that is characteristic of neurodegenerative disorders such as AD, PD, Wilson’s disease and Menkes disease. These metals are important in numerous biological processes in the brain and their homeostasis is regulated through multiple mechanisms of transport, storage, and secretion. The vertebrate divalent metal transporter-1 (DMT-1) has been implicated in transport and homeostasis of these divalent cations. In these studies I utilize Caenorhabditis elegans (C. elegans) to show that long term exposure to Mn2+ decreases animal viability in a dose-dependent manner, and I demonstrate that C. elegans homologues to DMT-1, SMF-1, SMF-2, and SMF-3, play specific roles in divalent metal ion-induced DA neurodegeneration. I show that SMF-1 contributes to Fe2+-induced DA neuron degeneration, SMF-3 contributes to Al3+-induced DA neuron degeneration, and both SMF-2 and DAT-1 contribute to Cu2+-induced DA neuron cell death. These studies utilize C. elegans as a powerful model to characterize molecules and pathways involved in metal toxicity and metal-induced DA neuron degeneration.