scholarly journals Peripheral Clock System Abnormalities in Patients With Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Tianbai Li ◽  
Cheng Cheng ◽  
Congcong Jia ◽  
Yue Leng ◽  
Jin Qian ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clock Genes ◽  
Large Population ◽  
Enzyme Linked Immunosorbent Assay ◽  
Altered Expression ◽  
Melatonin Concentration ◽  
Expression Levels ◽  
Plasma Melatonin ◽  
Peripheral Clock

Objective: To evaluate the altered expression of peripheral clock genes, circulating melatonin levels, and their correlations with sleep-wake phenotypes including probable rapid eye movement sleep behavior disorder (pRBD) symptoms in a relatively large population of Parkinson’s disease (PD) patients.Methods: We determined the expression profiles of five principal clock genes, BMAL1, CLOCK, CRY1, PER1, and PER2, in the peripheral blood mononuclear cells (PBMCs) of PD patients (n = 326), and healthy controls (HC, n = 314) using quantitative real-time PCR. Melatonin concentration in the plasma of two groups was evaluated by enzyme-linked immunosorbent assay. Then we performed comprehensive association analyses on the PBMCs clock gene expression, plasma melatonin levels and sleep characteristics.Results: Our data showed that the expression levels of BMAL1, CLOCK, CRY1, PER1, and PER2 were significantly decreased in the PBMCs of PD as compared with that of HC (P < 0.05). PD patients had reduced plasma melatonin levels compared with HC (P < 0.0001). pRBD and excessive daytime sleepiness are common in these PD patients and are associated with the expression levels of all five clock genes (r = −0.344∼−0.789, P < 0.01) and melatonin concentration (r = −0.509∼−0.753, P < 0.01). Statistical analyses also revealed that a combination of five clock genes and melatonin could reach a high diagnostic performance (areas under the curves, 97%) for PD comorbid pRBD.Conclusion: This case-control study demonstrates that peripheral BMAL1, CLOCK, CRY1, PER1, PER2, and melatonin levels are altered in PD patients and may serve as endogenous markers for sleep and wakefulness disturbances of PD.

Neuroprotective Effects of a GLP-2 Analogue in the MPTP Parkinson’s Disease Mouse Model

2021 ◽  
pp. 1-15
Author(s):  
Zijuan Zhang ◽  
Li Hao ◽  
Ming Shi ◽  
Ziyang Yu ◽  
Simai Shao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Dual Agonist

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

scholarly journals The Relationship Between Serum Levels of lncRNA H19, GAS5, HAR1B, LINC01783 and Clinical Signs of Parkinson's Disease

2021 ◽  
Author(s):  
Betul Ozdilek ◽  
Ibrahim Alper Kaya ◽  
Berna Demircan ◽  
Temel Tombul ◽  
Handan Ankarali
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Venous Blood ◽  
Clinical Signs ◽  
Serum Levels ◽  
Healthy Controls ◽  
Altered Expression ◽  
Expression Levels ◽  
Significant Difference

Abstract Long noncoding RNAs (lncRNAs) are highly expressed in brain and alterations in their levels have been shown in many neurodegenerative disorders. Evidence has shown that lncRNAs play role in the onset and progression of Parkinson’s disease (PD) and it can be used as a potential therapeutic target for the disease. In this study, we aimed to detect whether the serum expression levels of four candidate lncRNAs; H19, GAS5, HAR1B and LINC01783 are related with the clinical findings and treatment of PD or not. 83 patients and 50 healthy controls, matching in age and gender, are included in this study. We assessed how severe the disease is, by using the Hoehn Yahr (HY) staging and the Unified PD rating scale (UPDRS). Venous blood samples were taken from the participants. Serum samples were centrifuged and stored at -80°C until analysis. Expression levels of these lncRNAs were analyzed by a real-time PCR instrument in the laboratory. Statistical analysis of the data was performed using SPSS program. There was no significant difference between the PD patients and healthy controls in these lncRNAs serum levels. Age, gender, education level, presence of hypertension, type of onset of the disease and predominance of the right and left side, disease duration and treatment did not differ in lncRNA expression levels. Solely, there was a significant negative correlation between GAS5 and HY and UPDRS scores. Patients with family history had significantly higher levels of LINC01783. This is the first comprehensive study on lncRNAs in Turkish patients with PD. If any altered expression levels of these four lncRNAs were shown in the serum, it would provide an easy way to analyze underlying pathogenesis of the disease and contribute the possible biomarkers of PD.

THE ROLE OF CIRCADIAN REGULATION OF GHRELIN LEVELS IN PARKINSON’S DISEASE (LITERATURE REVIEW)

2021 ◽  
Vol 74 (7) ◽  
pp. 1750-1753
Author(s):  
Kateryna A. Tarianyk ◽  
Nataliya V. Lytvynenko ◽  
Anastasiia D. Shkodina ◽  
Igor P. Kaidashev
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clock Genes ◽  
Biological Rhythms ◽  
Circadian Regulation ◽  
Diurnal Changes ◽  
Dopaminergic Therapy ◽  
Peripheral Oscillators ◽  
Genes Expression

The paper is aimed at the analysis of the role of the circadian regulation of ghrelin levels in patients with Parkinson’s disease. Based on the literature data, patients with Parkinson’s disease have clinical fluctuations in the symptoms of the disease, manifested by the diurnal changes in motor activity, autonomic functions, sleep-wake cycle, visual function, and the efficacy of dopaminergic therapy. Biological rhythms are controlled by central and peripheral oscillators which links with dopaminergic neurotransmission – core of the pathogenesis of Parkinson`s disease. Circadian system is altered in Parkinson`s disease due to that ghrelin fluctuations may be changed. Ghrelin is potential food-entrainable oscillator because it is linked with clock genes expression. In Parkinson`s disease this hormone may induce eating behavior changing and as a result metabolic disorder. The “hunger hormone” ghrelin can be a biomarker of the Parkinson’s disease, and the study of its role in the pathogenesis, as well as its dependence on the period of the day, intake of levodopa medications to improve the effectiveness of treatment is promising.

scholarly journals Evaluation of Serum Apolipoprotein E as a Potential Biomarker for Pharmacological Therapeutic Efficacy Monitoring in Dopamine Dictated Disease Spectrum of Schizophrenia and Parkinson’s disease: A Preliminary Study

2018 ◽  
Vol 10 ◽  
pp. 117957351880358 ◽  
Author(s):  
Ashish Kumar Gupta ◽  
Komal Rani ◽  
Surabhi Swarnkar ◽  
Gaurav Khunger Kumar ◽  
Mohd Imran Khan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Apolipoprotein E ◽  
Pharmacological Intervention ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease States ◽  
Disease Spectrum ◽  
Potential Biomarker ◽  
Schizophrenic Patients ◽  
The Right

Aim of the Study: Parkinson’s disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson’s disease and schizophrenia for optimum therapy. Methods: Naïve and treated, Parkinson’s disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson’s disease and schizophrenia. Results: Apolipoprotein E levels are higher in Parkinson’s disease patients as compared with schizophrenic samples ( P < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson’s disease and schizophrenia in the right perspective. Conclusion: Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson’s disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.

scholarly journals An ensemble feature selection framework for early detection of Parkinson's disease based on feature correlation analysis

2021 ◽  
Author(s):  
Sarfaraz Masood ◽  
Khwaja Wisal ◽  
Om Pal ◽  
Chanchal Kumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Feature Selection ◽  
Large Population ◽  
Feature Selection Method ◽  
Sampling Strategy ◽  
Chi Square ◽  
Accurate Identification ◽  
Initial Symptoms ◽  
Selection Framework

Parkinson’s disease (PD) is a highly common neurological disease affecting a large population worldwide. Several studies revealed that the degradation of voice is one of its initial symptoms, which is also known as dysarthria. In this work, we attempt to explore and harness the correlation between various features in the voice samples observed in PD subjects. To do so, a novel two-level ensemble-based feature selection method has been proposed, whose results were combined with an MLP based classifier using K-fold cross-validation as the re-sampling strategy. Three separate benchmark datasets of voice samples were used for the experimentation work. Results strongly suggest that the proposed feature selection framework helps in identifying an optimal set of features which further helps in highly accurate identification of PD patients using a Multi-Layer Perceptron from their voice samples. The proposed model achieves an overall accuracy of 98.3%, 95.1% and 100% on the three selected datasets respectively. These results are significantly better than those achieved by a non-feature selection based option, and even the recently proposed chi-square based feature selection option.

scholarly journals Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Yui Nakayama ◽  
Satoru Morimoto ◽  
Misao Yoneda ◽  
Shigeki Kuzuhara ◽  
Yasumasa Kokubo
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Phosphorylated Tau ◽  
Total Tau ◽  
Lateral Sclerosis

Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (), Alzheimer’s disease (), Parkinson’s disease (), amyotrophic lateral sclerosis (), and controls () using specific enzyme-linked immunosorbent assay methods. Results. Total tau and phosphorylated tau did not increase and amyloid β42 was relatively reduced in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid β42 might discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from amyotrophic lateral sclerosis and Parkinson’s disease, and the ratios of phosphorylated-tau to amyloid β42 could discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease. Conclusions. Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease.

Protective effect of hydralazine on a cellular model of Parkinson’s disease: a possible role of hypoxia-inducible factor (HIF)-1α

2020 ◽  
Vol 98 (3) ◽  
pp. 405-414 ◽  
Author(s):  
Mehrnaz Mehrabani ◽  
Mohammad Hadi Nematollahi ◽  
Mojde Esmaeili Tarzi ◽  
Kobra Bahrampour Juybari ◽  
Moslem Abolhassani ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Antioxidant Power ◽  
Expression Levels ◽  
Downstream Target ◽  
Protein Levels ◽  
Ferric Reducing Antioxidant Power ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disease accompanied by a low expression level of cerebral hypoxia-inducible factor (HIF-1α). Hence, activating the hypoxia-signaling pathway may be a favorable therapeutic approach for curing PD. This study explored the efficacy of hydralazine, a well-known antihypertensive agent, for restoring the impaired HIF-1 signaling in PD, with the aid of 6-hydroxydopamine (6-OHDA)-exposed SH-SY5Y cells. The cytotoxicity of hydralazine and 6-OHDA on the SH-SY5Y cells were evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and apoptosis detection assays. The activities of malondialdehyde, nitric oxide (NO), ferric reducing antioxidant power (FRAP), and superoxide dismutase (SOD) were also measured. Expression levels of HIF-1α and its downstream genes at the protein level were assessed by Western blotting. Hydralazine showed no toxic effects on SH-SY5Y cells, at the concentration of ≤50 μmol/L. Hydralazine decreased the levels of apoptosis, malondialdehyde, and NO, and increased the activities of FRAP and SOD in cells exposed to 6-OHDA. Furthermore, hydralazine up-regulated the protein expression levels of HIF-1α, vascular endothelial growth factor, tyrosine hydroxylase, and dopamine transporter in the cells also exposed to 6-OHDA, by comparison with the cells exposed to 6-OHDA alone. In summary, hydralazine priming could attenuate the deleterious effects of 6-OHDA on SH-SY5Y cells by increasing cellular antioxidant capacity, as well as the protein levels of HIF-1α and its downstream target genes.

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