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The role of well water and other factors in the aetiology of Parkinson's diseaseBen-Shlomo, Yoav January 2004 (has links)
Objectives: To determine the risk of early onset Parkinson's disease (PD) associated with well water consumption and other risk factors. Design: A case control study with strata matching by age group, gender and current urban or rural residence. Setting: Republic of Ireland, between 1993 to 1995. Participants: Cases with Parkinson's disease, fulfilling at least two of the four cardinal features, with date of birth from 1st January 1926 and disease onset before 56 years. Controls were selected using stratified random sampling from the electoral register. Outcome measures: Odds ratio and 95% confidence interval for well water consumption and other risk factors. Results: Increased risk was associated with well water consumption (odds ratio per 20 years exposure 1.33, 95% CI 1.00 to 1.77), family history of PD (odds ratio 2.15, 95% CI 1.09 to 4.27), and serious head injury (odds ratio 3.08, 95% CI 1.66 to 5.71). Decreased risk was associated with childhood contact with a dog (odds ratio 0.44, 0.25 to 0.78), recall of chicken pox (odds ratio 0.51, 95% CI 0.32 to 0.83), smoking status (odds ratio for 30 or more pack years for smokers 0.19, 95% CI 0.07 to 0.57), exposure to insecticides (odds ratio 0.44, 95% CI 0.25 to 0.77), glue (odds ratio 0.52, 95% CI 0.29 to 0.93), paints (odds ratio 0.37, 95% CI 0.22 to 0.60) and cumulative socioeconomic position (odds ratio for a point reduction in socioeconomic position 0.74, 95% CI 0.61 to 0.90). Conclusions: These results have identified a wide range of exposures from childhood to adulthood that may influence the risk of PD across the life course. Because of potential biases, it is important that these results are replicated in other designs such as occupational or population based cohort studies.
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Investigating mechanisms involved in α-synuclein axonal transportHill, Josephine Elizabeth January 2004 (has links)
No description available.
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Saturn's atmosphere : Functional analysis of α-synuclein using RNAi-mediated knockdown in human neuronal cellsFountaine, Timothy January 2007 (has links)
No description available.
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Occupational and environmental risk factors for Parkinson's diseaseDick, Smita January 2005 (has links)
Case-control study or prevalent parkinsonism and PD cases in Grampian and Easter Ross, Scotland. Cases were defined using United Kingdom Parkinson's Disease Society Brain Bank clinical diagnostic criteria. Dementia, cerebrovascular and drug-induced cases were excluded. Age and gender-balanced controls were drawn from hospital outpatients and the community. Trained interviewers administered a questionnaire regarding lifestyle and occupation including solvent, pesticide and metal exposure (iron, copper, manganese). An occupational hygienist estimated metal exposures blind to disease status using a job exposure matrix modified by subjective exposure estimation. Lifetime occupational histories were classified by occupational (Dictionary of Occupational Titles) and industry (modified International Standard Industrial Classification. A follow-up postal study in Grampian enquired about tea and coffee consumption, anxiolytic, anti-depressant and hypnotic use and head injury. 202 cases and 420 controls were recruited between June 2000 and July 2002 (responsive rate 46.2%). Multiple logistic regression analyses showed first-degree family history of PD (OR 4.12, 95%CI 1.92-8.83) and pesticides ('high' exposure OR 1.69, 95% CI 1.06-2.69) were risk factors. Smoking was protective (OR 0.26, 95%CI 0.18-0.29) with an exposure-response relationship. Both occupational and industry coding systems showed non-significantly increased risks for 'agriculture'. The follow-up study response rate was 93% (149 cases, 305 controls). Tea and coffee consumption were not associated with PD. A positive association of use of psychoactive medication with PD was probably explained by their use after disease onset. A non-significantly increased association of head injury and PD was not supported by the follow-up postal study. First-degree family history of PD was associated with PD. Pesticide use was a risk factor for PD, whereas smoking was associated with reduced risk. The increased risk for agriculture may reflect pesticide use.
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The effects of Parkinson's disease mimetics on the proteasomal and neurofilament systems in SH-SY5Y cellsCaneda-Ferrón, B. January 2006 (has links)
Mitochondrial impairment, glutathione depletion and oxidative stress have been implicated in the pathogenesis of Parkinson's disease, linked recently to proteasomal dysfunction. This study analyses how these factors influence the various activities of the proteasome in SH-SY5Y human neuroblastoma cells treated with the PD mimetics MPP+ (a complex I inhibitor) or dopamine. Treatment with these toxins led to dose and time dependent reductions in ATP and glutathione levels and also chymotrypsin-like and postacidic-like activities; however, trypsin-like activity was unaffected. Antioxidants blocked the effects of dopamine but not MPP+, suggesting that oxidative stress was more important in the dopamine-mediated effects. With MPP+, ATP depletion was a pre-requisite for loss of proteasomal function. This study also shows that addition of MPP+ or dopamine to purified samples of the human 20S proteasome also reduced proteasomal activities; with dopamine being most damaging. As was the case with toxin-treated cells chymotrypsin-like activity was the most sensitive and trypsin-like activity, the least sensitive. The direct effect of both compounds on proteasomal activity was, at least, partly due to oxidative damage to the proteasome, since the antioxidant vitamin C could partially alleviate the proteasomal impairment. Indeed, Western blot analyses showed that some of the ?- and ?-subunits of the proteasome were modified by dopamine treatment. One of the hallmarks of Parkinson's disease is the appearance of Lewy bodies, which are protein inclusions containing ?-synuclein, neurofilament proteins and ubiquitinated proteins. A growing body of evidence suggests that the UPS might be involved in the formation of these aggregates. This thesis, reports that neurofilaments can undergo proteasomal degradation and that MPP+ and dopamine alter the expression/phosphorylation and distribution of these cytoskeletal proteins in SH-SY5Y cells. Therefore aberrant changes in both neurofilament profiles and proteasomal degradation may influence inclusion formation in dopaminergic neurons.
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Analysis of mutations in alpha-synuclein and the protective effect of heat shock proteins in a model of alpha-synuclein-induced toxicityZourlidou, Alexandra January 2005 (has links)
Genetic studies have revealed three mutations (A30P, A53T and E46K) in alpha-synuclein (alpha-Syn) that cause Parkinson's disease (PD) in a small number of pedigrees with autosomal dominant inheritance. For the purpose of this thesis an in vitro model has been developed by stably over-expressing wild type (wt), A30P or A53T mutant alpha-Syn in ND7 neuronal cells. Wt alpha-Syn can enhance cell death in response to ischaemia/reoxygenation or staurosporine treatment whilst protecting against serum removal and dopamine-induced cell death in this system. In contrast, both mutant forms of alpha-Syn enhance cell death. The above stresses were used to induce primarily apoptotic cell death, implicated in PD pathology. Hence, the PD-associated mutations convert alpha-Syn from a protein which could modulate cell death differently in different circumstances to forms which are deleterious in response to various stresses. Subsequently, the neuroprotective effect of various heat shock proteins (hsps) in the above system was studied, utilising a Herpes Simplex Virus-based gene delivery system. For the first time, it was demonstrated that in an in vitro mammalian model of alpha-Syn-induced toxicity over-expression of hsp27 protects, under all the stresses tested, both wt and mutant alpha-Syn expressing cells, as assessed by multiple apoptotic/necrotic death assays. Interestingly, A30P alpha-Syn expressing cells were markedly protected by caspase-8 and caspase-9 inhibition as well as by hsp27 over-expression. No synergy between hsp27 and the caspase inhibitors was observed. In addition, hsp70 conferred protection only to wt alpha-Syn expressing cells exposed to ischaemia whereas hsp56 had no protective role in this system. Hence, hsp27 was neuroprotective by interfering with the enhanced caspase-dependent cell death resulting from mutant A30P alpha-Syn over-expression. Finally, studies of the mitochondrial status in this system were performed to further explore the site of action of hsp27. Hsp27 reduced significantly the mitochondrial membrane potential loss in stressed A30P mutant alpha-Syn cells and this correlates well with their enhanced cell survival. These findings suggest that hsp27 has a novel neuroprotective role against mutant alpha-Syn toxicity and this is achieved by interfering with the caspase cascade and mechanisms modulating the mitochondrial membrane potential.
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What is the relationship between clinical phenotype and the development of dementia in idiopathic Parkinson's disease?Dunn, Edward Michael January 2004 (has links)
No description available.
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PET studies on the aetiology of Parkinson's disease and on the efficacy of cell transplantation therapyPiccini, Paola January 2005 (has links)
No description available.
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Psychological outcome in people with Parkinson’s disease and their spouses : the effect of motor fluctuationsTalbot, Louise January 2005 (has links)
No description available.
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The role of alpha synuclein in Parkinson's diseaseMoualla, Dima January 2011 (has links)
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. It is characterized by the presence of intracellular inclusions termed Lewy bodies (LBs) and Lewy neuritis (LNs) in the brain, in which α-Syn aggregates constitute the main component. Therefore, α-Syn aggregation was implicated in the pathogenesis of PD. Structurally α-Syn is a disordered protein with little ordered structure under physiological conditions. However, research of α-Syn has provided substantial information about its structural properties. The precise function of α-Syn is still under investigation. Research has also shown that metals, such as copper and iron, accelerate α-Syn aggregation and fibrillation in vitro and are proposed to play an important role in vitro. In this study, isothermal titration calorimetry was used to determine iron binding properties to α-Syn revealing the presence of two binding sites for iron with an affinity of 1.06 x 105 M-1 and a dissociation constant of ~ 10μM which is physiologically relevant to iron content in the brain. In addition, α-Syn was found to reduce iron in the presence of copper. This property was demonstrated via ferrozine based assay. In vitro, thoflavin-T fluorescence assay was used to investigate the mechanism by which metals induce α-Syn aggregation and whether it is related to metal binding. Metals, mainly copper and iron, caused 2-fold increase in the aggregation rate of WT α-Syn and its metal binding mutants. Linking that to the increased metal content in the brain, α-Syn aggregation can cause changes in tissue composition, thus altering the normal functional environment in the brain. Moreover, western blotting analysis showed that copper increases the aggregate formation in mammalian dopaminergic cells over-expressing α-Syn.
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