Expression Profiling of Blood microRNAs 885, 361, and 17 in the Patients with the Parkinson’s disease: Integrating Interaction Data to Uncover the Possible Triggering Age-Related Mechanisms

Abstract MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of the Parkinson’s disease (PD), an age related-neurodegenerative disorder. The aim of present study was to compare the expression profiles of a new set of candidate miRNAs related to aging and cellular senescence in peripheral blood mononuclear cells (PBMCs) obtained from the PD patients with healthy controls and then in the early and advanced stages of the PD patients with their controls to clarify whether their expression was correlated with the disease severity. We have also proposed a consensus-based strategy to interpret the miRNAs expression data to gain a better insight into the molecular regulatory alterations during the incidence of PD. We evaluated the miRNA expression levels in the PBMCs obtained from 36 patients with PD and 16 healthy controls by the reverse transcription-quantitative real-time PCR and their performance to discriminate the PD patients from the healthy subjects assessed using the receiver operating characteristic curve analysis. Also, we applied our consensus and integration approach to construct a deregulated miRNA-based network in PD with the respective targets and transcription factors, and the enriched gene ontology and pathways using the enrichment analysis approach were obtained. There was a significant overexpression of miR-885 and miR-17 and the downregulation of miR-361 in the PD patients compared to the controls. The blood expression of miR-885 and miR-17 tended to increase along with the disease severity. On the other hand, the lower levels of miR-361 in the early stages of the PD patients, as compared to controls, and its higher levels in the advanced stages of PD patients, as compared to the early stages of the PD patients, were observed. Combination of all three miRNAs showed an appropriate value of AUC (0.985) to discriminate the PD patients from the healthy subjects. Also, the deregulated miRNAs were linked to the known PD pathways and the candidate related target genes were presented. We revealed 3 candidate biomarkers related to aging and cellular senescence for the first time in the patients with PD. Our in-silico analysis identified candidate target genes and TFs, including those related to neurodegeneration and PD. Overall, our findings provided novel insights into the probable age-regulatory mechanisms underlying PD and a rationale to further clarify the role of the identified miRNAs in the PD pathogenesis.

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Reliability of using foot-worn devices to measure gait parameters in people with Parkinson’s disease

Neurorehabilitation ◽

10.3233/nre-210101 ◽

2021 ◽

pp. 1-8

Author(s):

Ya-Yun Lee ◽

Ming-Hao Li ◽

Jer-Junn Luh ◽

Chun-Hwei Tai

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Severity ◽

Wearable Sensors ◽

Good Reliability ◽

Retest Reliability ◽

Early Stages ◽

Gait Parameters ◽

Advanced Stages ◽

Test Retest Reliability

BACKGROUND: Recent advances in technology have warranted the use of wearable sensors to monitor gait and posture. However, the psychometric properties of using wearable devices to measure gait-related outcomes have not been fully established in patients with Parkinson’s disease (PD). OBJECTIVE: This study aimed to investigate the test-retest reliability of body-worn sensors for gait evaluation in people with PD. Additionally, the influence of disease severity on the reliability was determined. METHODS: Twenty individuals with PD were recruited. During the first evaluation, the participants wore inertial sensors on their shoes and walked along a walkway thrice at their comfortable walking speed. The participants were then required to return to the lab after 3–5 days to complete the second evaluation with the same study procedure. Test-retest reliability of gait-related outcomes were calculated. To determine whether the results would be affected by disease severity, reliability was re-calculated by subdividing the participants into early and mid-advanced stages of the disease. RESULTS: The results showed moderate to good reliability (ICC = 0.64–0.87) of the wearable sensors for gait assessment in the general population with PD. Subgroup analysis showed that the reliability was higher among patients at early stages (ICC = 0.71–0.97) compared to those at mid-advanced stages (ICC = 0.65–0.81) of PD. CONCLUSIONS: Wearable sensors could reliably measure gait parameters in people with PD, and the reliability was higher among individuals at early stages of the disease compared to those at mid-advanced stages. Absolute reliability values were calculated to act as references for future studies.

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α-Synuclein oligomers in skin biopsy of idiopathic and monozygotic twin patients with Parkinson’s disease

Brain ◽

10.1093/brain/awaa008 ◽

2020 ◽

Vol 143 (3) ◽

pp. 920-931 ◽

Cited By ~ 5

Author(s):

Samanta Mazzetti ◽

Milo J Basellini ◽

Valentina Ferri ◽

Erica Cassani ◽

Emanuele Cereda ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Nervous System ◽

Peripheral Nervous System ◽

Genetic Predisposition ◽

Healthy Subjects ◽

Proximity Ligation Assay ◽

Healthy Controls ◽

Proximity Ligation ◽

Synaptic Terminals

Abstract A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson’s disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson’s disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson’s disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson’s disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson’s disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson’s disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.

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Work and power reduced in L-dopa naïve patients in the early-stages of Parkinson’s disease

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20160014 ◽

2016 ◽

Vol 74 (4) ◽

pp. 287-292

Author(s):

Lidiane Oliveira Lima ◽

Francisco Cardoso ◽

Luci Fuscaldi Teixeira-Salmela ◽

Fátima Rodrigues-de-Paula

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Healthy Subjects ◽

Lower Limbs ◽

Control Group ◽

Isokinetic Dynamometer ◽

Muscular Performance ◽

Early Stages ◽

Rehabilitation Strategies

ABSTRACT Studies which have investigated muscular performance during the initial stages of Parkinson´s disease (PD) without L-dopa treatments were not found. Objective to assess whether muscular performance, work and power, of the trunk and lower limbs in L-dopa naïve patients in the early stages of PD was lower than those of healthy subjects and to compare muscular performance between the lower limbs. Method Ten subjects with PD, Hoehn and Yahr (HY) I-II, L-dopa naïve and 10 subjects in the control group were assessed with the isokinetic dynamometer. Results ANOVAs revealed that work and power measures of the trunk, hip, knee, and ankle muscular groups were lower in PD compared with the control group (p < 0.05). There were no significant differences in muscular performance between the lower limbs. Conclusion The results suggested the use of specific exercises, as rehabilitation strategies, to improve the ability to produce work and power with this population.

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Sudden unexpected death in Parkinson’s disease: why is drinking water important?

Neurodegenerative Disease Management ◽

10.2217/nmt-2019-0010 ◽

2019 ◽

Vol 9 (4) ◽

pp. 241-246 ◽

Cited By ~ 1

Author(s):

Francisco S Menezes-Rodrigues ◽

Cristiane S Scorza ◽

Ana C Fiorini ◽

Afonso Caricati-Neto ◽

Carla A Scorza ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Drinking Water ◽

Neurodegenerative Disorders ◽

Premature Death ◽

Healthy Controls ◽

Unexpected Death ◽

Age Related ◽

Daily Water ◽

Daily Water Consumption

Parkinson’s disease (PD) is one of the most common age-related neurodegenerative disorders. Several studies over the last few years have shown that PD is accompanied by high rates of premature death compared with healthy controls. Death in PD patients is usually caused by determinant factors such as pneumonia, and cerebrovascular and cardiovascular diseases. During recent years it has emerged that dehydration may also contribute to mortality in PD. Interestingly, it has been documented that a substantial proportion of patients with PD die suddenly (known as sudden and unexpected death in PD). In this article, we focus on the magnitude of the problem of sudden and unexpected death in PD, with special reference to the daily water consumption of PD patients.

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The activity of markers of oxidative and nitrosative stresses in blood plasma of Parkinson’s disease patients at the early stages

Pathologia ◽

10.14739/2310-1237.2021.2.233431 ◽

2021 ◽

Vol 18 (2) ◽

pp. 183-188

Author(s):

A. V. Demchenko ◽

V. V. Biriuk ◽

A. V. Abramov

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Blood Plasma ◽

Emotional Disorders ◽

Healthy Controls ◽

Early Stages ◽

Gpx Activity ◽

Gst Activity ◽

In Blood Plasma

The aim of the study is to investigate activity of markers of oxidative and nitrosative stresses in blood plasma of patients in the I–II stages of Parkinson’s disease (PD) and to determine correlations between their concentrations and severity of non-motor PD symptoms. Materials and methods. 67 patients at I–II PD stages and 20 healthy controls took part in the research. Cognitive functions were examined due to the Montreal Cognitive Assessment test – MoCA test. For the severity of psycho-emotional disorders evaluation the following scales and questionnaires were used: Night Sleep Assessment Questionnaire by A. M. Vein, Zung test for anxiety, apathy Starkstein scale, Boston stress-resistance test, Beck Depression Inventory (BDI-II). We performed ELISA test for determination of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and 3-nitrotyrosine (3-NT) level in blood plasma of participants (Elabscience® kit). Results. The middle age of PD patients and healthy controls was 64.35 ± 1.22 and 66.40 ± 0.70 years, respectively. GPx activity in plasma of patients at І–ІІ PD stages was significantly lower than in healthy controls (P < 0.001) and was higher at the I stage compared to the II PD stage (P = 0.003). Also GPx activity in PD patients with normal cognition was higher than in PD patients with cognitive impairment (P = 0.042). The GST activity in plasma of PD patients with anxiety was significantly lower (P = 0.002) compared to those without anxiety, and 3-NT blood plasma level in PD patients with moderate anxiety was higher than in those without one (P = 0.029). Conclusions. The activity of antioxidant GPx was significantly lower in PD patients at early stages compared to healthy controls, and in PD patients in the II stage of the disease compared to the I stage, and it was significantly lower in PD patients with cognitive impairment. PD patients with moderate anxiety had lower 3-NT levels and GST activity in blood plasma.

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Glutathione as a Biomarker in Parkinson’s Disease: Associations with Aging and Disease Severity

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/9409363 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 15

Author(s):

Laurie K. Mischley ◽

Leanna J. Standish ◽

Noel S. Weiss ◽

Jeannie M. Padowski ◽

Terrance J. Kavanagh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Severity ◽

Rating Scale ◽

Rank Order ◽

Correlation Coefficients ◽

Resonance Spectroscopy ◽

Cross Sectional ◽

Age Related ◽

Patient Reported

Objectives. Oxidative stress contributes to Parkinson’s disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity.Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross-sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman’s rank-order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient-Reported Outcomes in PD (PRO-PD) were used to rate disease severity using regression analysis.Results. Blood measures of Glu decreased with age, although there was no age-related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (P=0.02, 95% CI: −13.96, −1.14) and the PRO-PD (P=0.01, 95% CI: −0.83, −0.11) scores.Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes.

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Accuracy and Reliability of Onset Detection Algorithms in Gait Initiation for Healthy Controls and Participants With Parkinson’s Disease

Journal of Applied Biomechanics ◽

10.1123/jab.2018-0431 ◽

2019 ◽

Vol 35 (6) ◽

pp. 393-400

Author(s):

Aisha Chen ◽

Sandhya Selvaraj ◽

Vennila Krishnan ◽

Shadnaz Asgari

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Healthy Subjects ◽

Center Of Pressure ◽

Intraclass Correlation ◽

Gait Initiation ◽

Healthy Controls ◽

Onset Detection ◽

Detection Algorithms ◽

Absolute Reliability

Accurate and reliable detection of the onset of gait initiation is essential for the correct assessment of gait. Thus, this study was aimed at evaluation of the reliability and accuracy of 3 different center of pressure–based gait onset detection algorithms: A displacement baseline–based algorithm (method 1), a velocity baseline–based algorithm (method 2), and a velocity extrema–based algorithm (method 3). The center of pressure signal was obtained during 10 gait initiation trials from 16 healthy participants and 3 participants with Parkinson’s disease. Intrasession and absolute reliability of each algorithm was assessed using the intraclass correlation coefficient and the coefficient of variation of center of pressure displacement during the postural phase of gait initiation. The accuracy was evaluated using the time error of the detected onset by each algorithm relative to that of visual inspection. The authors’ results revealed that although all 3 algorithms had high to very high intrasession reliabilities in both healthy subjects and subjects with Parkinson’s disease, methods 2 and 3 showed significantly better absolute reliability than method 1 in healthy controls (P = .001). Furthermore, method 2 outperformed the other 2 algorithms in both healthy subjects and subjects with Parkinson’s disease with an overall accuracy of 0.80. Based on these results, the authors recommend using method 2 for accurate and reliable gait onset detection.

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Influence of Thoracoabdominal Movement on Pulmonary Function in Patients with Parkinson's Disease: Comparison with Healthy Subjects

Neurorehabilitation and Neural Repair ◽

10.1177/154596830001400105 ◽

2000 ◽

Vol 14 (1) ◽

pp. 43-47 ◽

Cited By ~ 10

Author(s):

Akira Tamaki ◽

Yoshimi Matsuo ◽

Takehiko Yanagihara ◽

Kazuo Abe

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pulmonary Function ◽

Forced Vital Capacity ◽

Healthy Subjects ◽

Vital Capacity ◽

Healthy Controls ◽

Pulmonary Dysfunction ◽

Average Volume ◽

Abdominal Movement

Patients with Parkinson's disease (PD) may develop pulmonary dysfunction, but the pathogenesis remains unclear. We investigated a correlation between thoracoab dominal movements and pulmonary function in seven patients with PD and 14 healthy controls. We measured vital capacity (VC) and forced vital capacity (FVC) using an autospirometer, and measured chest and abdominal movements using a respiraory in ductance plethysmography by fixing transducers on the rib cage and umbilicus. Pa tients with PD had significantly decreased % VC (90.3 ± 17.1 vs 105.8 ± 13.9%), chest movement (271.3 ± 79.6 vs. 375.2 ± 126.7% VT) and abdominal movement (217.6 ± 93.5 vs. 247.4 ± 100.2% VT) with 100% VT being an average volume of chest and abdomen at rest during measurement of VC. Patients with PD also had sig nificantly decreased % FVC (74.4 ± 20.6 vs. 97.6 ± 14.1%), chest movement (246.2 ± 115.2 vs. 344.5 ± 126.4% VT) and abdominal movement (160.3 ± 105.6 vs 207.6 ± 104.7% VT) with 100% VT being an average volume of chest and abdomen at rest during forced maximal inspiration. Based on the results, we conclude that a reduction of % VC in patients with PD correlated with chest movements, while a reduction of % FVC correlated with ab dominal movement in patients with PD.

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Age-related changes in saccadic eye movements in healthy subjects and patients with Parkinson’s disease

Human Physiology ◽

10.1134/s0362119711010117 ◽

2011 ◽

Vol 37 (2) ◽

pp. 161-167 ◽

Cited By ~ 3

Author(s):

A. S. Litvinova ◽

P. O. Ratmanova ◽

E. I. Evina ◽

R. R. Bogdanov ◽

A. N. Kunitsyna ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Eye Movements ◽

Healthy Subjects ◽

Saccadic Eye Movements ◽

Age Related ◽

Age Related Changes

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The effects of virtual reality on functional capacity at different stages of Parkison’s disease

10.5327/1516-3180.466 ◽

2021 ◽

Author(s):

Yuri Sena Melo ◽

Wesley Anderson de Souza Miranda ◽

João Lucas De Morais Bezerra ◽

Thaís Bel de Oliveira Teixeira

Keyword(s):

Systematic Review ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Virtual Reality ◽

Functional Capacity ◽

Video Game ◽

Early Stages ◽

Yahr Scale ◽

Advanced Stages

Introduction: the use of virtual reality in Parkinson’s disease is a very effective therapy, as it promotes important actions for the knowledge of the motor, stimulating neuroplasticity, through visual feedback. Study design: This is a systematic review of the literature. Objective: The objective of this study was to analyze the use of reality in the rehabilitation of functional capacity in the different stages of Parkinson’s disease. Methods: this is a systematic review, carried out from January to August 2017, by means of electronic search in the databases: Pubmed, Scielo, Lilacs, Science Direct and Medline. The descriptors used were: virtual, video game, Parkinson’s, physiotherapy and rehabilitation and all the words in English. They were defined as inclusion criteria for studies that used virtual reality as treatment for patients with Parkinson’s, classifying patients in stages (I, II, III, IV and V) according to the Hoehn & Yahr scale. Literature review articles, description of virtual reality without showing the sample of statistical results and case study were excluded. Results: 7 articles were selected. After analyzing them, it was possible to observe that patients in the early stages showed improvement in perception, gait and balance. However, patients who were in other more advanced stages of the disease only improved their perception. Conclusion: patients in the early stages of clinical Parkinson’s disease have satisfactory results when compared to the advanced stages.

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