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Available from: PubMed Central
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ABSTRACT: There have been limited comparative data regarding the investigations on pulmonary and respiratory muscle function in the patients with different parkinsonism disorders such as Parkinson's disease (PD) and multiple system atrophy (MSA) versus normal elderly. The present study is aiming to characterize the performance of pulmonary function and respiratory muscle strength in PD and MSA, and to investigate the association with severity of motor symptoms and disease duration.
Pulmonary function and respiratory muscle strength tests were performed in 30 patients with PD, 27 with MSA as well as in 20 age-, sex-, height-, weight-matched normal elderly controls. All the patients underwent United Parkinson's disease rating scale (UPDRS) or united multiple system atrophy rating scale (UMSARS) separately as diagnosed.
Vital capacity, forced expiratory volume in 1 second and forced vital capacity decreased, residual volume and ratio of residual volume to total lung capacity increased in both PD and MSA groups compared to controls (p<0.05). Diffusing capacity was decreased in the MSA group, compared with PD and normal elderly control groups (p<0.05). Respiratory muscle strength was lower in both PD and MSA groups than in controls (p<0.05). The values representing spirometry function and respiratory muscle strength were found to have a negative linear correlation with mean score of UPDRS-III in PD and mean score of UMSARS-I in MSA. Respiratory muscle strength showed a negative linear correlation with the mean score of UMSARS-II and disease duration in MSA patients.
These findings suggest that respiratory dysfunction is involved in PD and MSA. Respiratory muscle strength is remarkably reduced, and some of the parameters correlate with disease duration and illness severity. The compromised respiratory function in neurodegenerative disorders should be the focus of further researches.
PLoS ONE 12/2014; 9(12):e116123. DOI:10.1371/journal.pone.0116123
Available from: Günter U Höglinger
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ABSTRACT: Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by intracellular aggregation of the microtubule-associated protein tau. The tau protein exists in 6 predominant isoforms. Depending on alternative splicing of exon 10, three of these isoforms have four microtubule-binding repeat domains (4R), whilst the others only have three (3R). In PSP there is an excess of the 4R tau isoforms, which are thought to contribute significantly to the pathological process. The cause of this 4R increase is so far unknown. Several lines of evidence link mitochondrial complex I inhibition to the pathogenesis of PSP. We demonstrate here for the first time that annonacin and MPP+, two prototypical mitochondrial complex I inhibitors, increase the 4R isoforms of tau in human neurons. We show that the splicing factor SRSF2 is necessary to increase 4R tau with complex I inhibition. We also found SRSF2, as well as another tau splicing factor, TRA2B, to be increased in brains of PSP patients. Thereby, we provide new evidence that mitochondrial complex I inhibition may contribute as an upstream event to the pathogenesis of PSP and suggest that splicing factors may represent an attractive therapeutic target to intervene in the disease process.
PLoS ONE 11/2014; 9(11):e113070. DOI:10.1371/journal.pone.0113070
Available from: Leo Ota
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ABSTRACT: Walking is generated by the interaction between neural rhythmic and physical activities. In fact, Parkinson's disease (PD), which is an example of disease, causes not only neural rhythm generation disorders but also physical disabilities. However, the relationship between neural rhythm generation disorders and physical disabilities has not been determined. The aim of this study was to identify the mechanism of gait rhythm generation. In former research, neural rhythm generation disorders in PD patients' walking were characterized by stride intervals, which are more variable and fluctuate randomly. The variability and fluctuation property were quantified using the coefficient of variation (CV) and scaling exponent a. Conversely, because walking is a dynamic process, postural reflex disorder (PRD) is considered the best way to estimate physical disabilities in walking. Therefore, we classified the severity of PRD using CV and a. Specifically, PD patients and healthy elderly were classified into three groups: no-PRD, mild-PRD, and obvious-PRD. We compared the contributions of CV and a to the accuracy of this classification. In this study, 45 PD patients and 17 healthy elderly people walked 200 m. The severity of PRD was determined using the modified Hoehn–Yahr scale (mH-Y). People with mH-Y scores of 2.5 and 3 had mild-PRD and obvious-PRD, respectively. As a result, CV differentiated no-PRD from PRD, indicating the correlation between CV and PRD. Considering that PRD is independent of neural rhythm generation, this result suggests the existence of feedback process from physical activities to neural rhythmic activities. Moreover, a differentiated obvious-PRD from mild-PRD. Considering a reflects the intensity of interaction between factors, this result suggests the change of the interaction. Therefore, the interaction between neural rhythmic and physical activities is thought to plays an important role for gait rhythm generation. These characteristics have potential to evaluate the symptoms of PD. Copyright: ß 2014 Ota et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
PLoS ONE 11/2014; 9(11):e112952. DOI:10.1371/journal.pone.0112952
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