scholarly journals Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rita Maszlag-Török ◽  
Fanni A. Boros ◽  
László Vécsei ◽  
Péter Klivényi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Blood ◽  
Histone Deacetylases ◽  
Mrna Level ◽  
Control Group ◽  
Mrna Levels ◽  
Cellular Functions ◽  
Hungarian Population ◽  
The Difference

AbstractParkinson’s disease (PD) is a neurodegenerative disease caused by complex interaction between genetic and environmental factors. There is a growing body of evidence of the involvement of sirtuins (SIRTs) in disease pathomechanism. SIRTs are NAD+-dependent histone deacetylases which take part in various cellular functions. However, available data of the relationship between SIRT gene polymorphisms and PD is limited. Our aim was to investigate the possible association of 10 SNPs identified within non-mitochondrial SIRTs, SIRT1, -2 and -6 with the risk of PD in Hungarian population, and to compare the expression level of these SIRTs between healthy controls and PD patients. Our results showed that rs3740051 and rs3818292 of SIRT1 and rs350843, rs350844, rs107251, rs350845 and rs350846 of SIRT6 show weak association with PD risk. On the contrary rs12778366 and rs3758391 of SIRT1 and rs10410544 of SIRT2 did not show association with PD. Moreover, we detected that mRNA level of SIRT1 was down-regulated, and mRNA level of SIRT6 was up-regulated, while SIRT2 mRNA level was not altered in the peripheral blood of PD patients as compared to controls. The difference in both cases was more pronounced when comparing the early-onset PD group to the control cohort. Nevertheless, mRNA level changes did not show any association with the presence of any of the investigated SNPs either in the PD or in the control group. In conclusion, our findings suggest that non-mitochondrial sirtuins, SIRT1 and -6 but not SIRT2 might contribute to the pathogenesis of PD in the Hungarian population both via their altered mRNA levels and via gene alterations identified as specific SNPs.

scholarly journals Potential Biomarkers of the Earliest Clinical Stages of Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Anelya Kh. Alieva ◽  
Elena V. Filatova ◽  
Aleksey V. Karabanov ◽  
Sergey N. Illarioshkin ◽  
Petr A. Slominsky ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reverse Transcription ◽  
Real Time Pcr ◽  
Peripheral Blood ◽  
Neurodegenerative Disorder ◽  
Mrna Levels ◽  
Clinical Stages ◽  
Specific Increase ◽  
Potential Biomarkers

Parkinson’s disease (PD) is a widespread neurodegenerative disorder. Despite the intensive studies of this pathology, in general, the picture of the etiopathogenesis has still not been clarified fully. To understand better the mechanisms underlying the pathogenesis of PD, we analyzed the expression of 10 genes in the peripheral blood of treated and untreated patients with PD. 35 untreated patients with PD and 12 treated patients with Parkinson’s disease (Hoehn and Yahr scores 1-2) were studied. An analysis of the mRNA levels ofATP13A2,PARK2,PARK7,PINK1,LRRK2,SNCA,ALDH1A1,PDHB,PPARGC1A, andZNF746genes in the peripheral blood of patients was carried out using reverse transcription followed by real-time PCR. A statistically significant and specific increase by more than 1.5-fold in the expression of theATP13A2,PARK7, andZNF746genes was observed in patients with PD. Based on these results, it can be suggested that the upregulation of the mRNA levels ofATP13A2,PARK7, andZNF746in untreated patients in the earliest clinical stages can also be observed in the preclinical stages of PD, and that these genes can be considered as potential biomarkers of the preclinical stage of PD.

scholarly journals Outcomes of primary total knee arthroplasty in patients with Parkinson’s disease: A Case Control Comparison Study

2017 ◽  
Vol 5 (5_suppl5) ◽  
pp. 2325967117S0020
Author(s):  
David Parker ◽  
Eugene Wong
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Range Of Motion ◽  
Primary Total Knee Arthroplasty ◽  
Control Group ◽  
Range Of Movement ◽  
Superficial Infection ◽  
Total Knee ◽  
The Difference

Introduction and Aims: There is considerable debate and a paucity of evidence regarding whether Total Knee Replacement (TKR) is of benefit in patients with Parkinson’s disease (PD) and knee osteoarthritis, and whether PD would compromise the outcome of TKR. Therefore, we aimed to compare the effect of TKR on range of motion and Oxford Knee Scores (OKS) between PD patients and age-matched controls at 1 year follow-up. Methods: A cohort of 45 knees from 35 patients was identified as having a confirmed diagnosis of Parkinson’s disease and received a primary TKR between January 2004 and December 2015, which was extracted from a clinical database (Socrates, v3.5, Orthosoft, AUS) maintained by two orthopaedic surgeons in two hospitals. An age-matched control group (mean age: 73 years) of 45 knees from 41 patients without Parkinson’s disease was randomly computer-generated from the same database. The indication for TKR in both groups was osteoarthritis, an independent assessment of each knee to meet appropriate selection criteria for TKR, as well as preoperative physician review for medical comorbidities. Outcome measures analysed in the study were the difference in pre-operative range of motion (RoM) and 12-point Oxford Knee Scores and at 1-year follow-up respectively. Postoperative complications and revisions were also recorded during the follow-up period. Results: In the PD group, RoM improved from a mean of 100 degrees preoperatively to 114 degrees at 12 months, compared to the control group which improved from a mean of 102 degrees to 114 degrees respectively. OKS in the Parkinson’s group improved from a mean of 23 preoperatively to 38 at 12 months compared to 23 preoperatively and 40 at 12 months in the control group. After adjusting for sex, we found that the difference in the ROM and OKS between the Parkinson’s and control groups was not significantly different (p = 0.9725; 0.6450 respectively). Furthermore, in all Parkinson’s patients the minimal clinically important difference for OKS (≥6) was achieved at 1-year follow-up (4). There were no mortalities during the study follow-up period, with 4 complications in the PD group (DVT, superficial infection) and two in the control group (DVT, bowel pseudo-obstruction). Conclusions: This study demonstrates that TKR provides comparable outcomes with regard to range of movement and ambulatory function in patients with Parkinson’s disease who are also suffering from severe osteoarthritis. We also feel that TKR has an acceptable complication profile in this subgroup of patients. The presence of PD does not appear to compromise the outcome of TKR in these patients, and the same indications for TKR should therefore apply as for the general OA population.

scholarly journals Aerobic Exercise Preserves Olfaction Function in Individuals with Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Anson B. Rosenfeldt ◽  
Tanujit Dey ◽  
Jay L. Alberts
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Aerobic Exercise ◽  
Exercise Program ◽  
Disease Process ◽  
Preliminary Evidence ◽  
Exercise Group ◽  
Systematic Evaluation ◽  
Control Group ◽  
The Difference

Introduction. Based on anecdotal reports of improved olfaction following aerobic exercise, the aim of this study was to evaluate the effects of an 8-week aerobic exercise program on olfaction function in individuals with Parkinson’s disease (PD).Methods. Thirty-eight participants with idiopathic PD were randomized to either an aerobic exercise group (n=23) or a nonexercise control group (n=15). The aerobic exercise group completed a 60-minute cycling session three times per week for eight weeks while the nonexercise control group received no intervention. All participants completed the University of Pennsylvania Smell Identification Test (UPSIT) at baseline, end of treatment, and a four-week follow up.Results. Change in UPSIT scores between the exercise and nonexercise groups from baseline to EOT (p=0.01) and from baseline to EOT+4 (p=0.02) favored the aerobic exercise group. Individuals in the nonexercise group had worsening olfaction function over time, while the exercise group was spared from decline.Discussion. The difference in UPSIT scores suggested that aerobic exercise may be altering central nervous system pathways that regulate the physiologic or cognitive processes controlling olfaction in individuals with PD. While these results provide promising preliminary evidence that exercise may modify the disease process, further systematic evaluation is necessary.

scholarly journals Neuroprotective Effects of Microfluidic Encapsulated Induced Conjunctival Mesenchymal Stem Cells Through Autophagy Modulation in a Parkinsonian Model

2021 ◽  
Author(s):  
Hossein Mostafavi ◽  
Meysam Forouzandeh ◽  
Mohammad Reza Bigdeli ◽  
Samad Nadri ◽  
Mehdi Eskandari
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Control Group ◽  
Mrna Levels ◽  
Significant Difference ◽  
Free Cells

Abstract Background and Aim: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreases rated of autophagy. According to recent studies, cell therapy has been attracted much attention for PD treatment. Due to the many advantages mesenchymal stem cells (MSCs) have proposed, they have been considered a valuable resource for PD cell therapy. The present study aimed to investigate the therapeutic effect of Conjunctival MSCs (CJ-MSCs) on the autophagy manner and the expression of Mammalian target of rapamycin (mTOR), TH, and α-Syn in the parkinsonian rat model.Materials and Methods: our investigation has been performed using the Parkinson's model of rats. Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs both encapsulated and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses have been carried out to evaluate the potency of CJ-MSCs (both encapsulated and free cells) on PD rats. The Rotation, Rotarod Open field test was recruited as the behavioral tests. Immunohistochemistry was used to determine the tyrosine hydroxylase (TH), and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) has been performed for investigating the α-Syn and mTOR gene expression.Results: Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. Immunohistochemistry analysis revealed an increase in the number of TH+ cells compared to the control group. The gene expression evaluation showed a significant reduction in mTOR and α-Syn mRNA levels than the control group. Our results also represented a significant difference between rats receiving encapsulated CJ-MSCs compared to the group received free CJ-MSCs.Conclusion: It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by reducing mTOR and thus increase TH expression that led improve the motor functions of rats. Our results indicated the CJ-MSCs as a suitable source of MSCs to reduce PD complications.

scholarly journals Differences in the Composition of Gut Microbiota between Patients with Parkinson’s Disease and Healthy Controls: A Cohort Study

2021 ◽  
Vol 10 (23) ◽  
pp. 5698
Author(s):  
Barbara Zapała ◽  
Tomasz Stefura ◽  
Magdalena Wójcik-Pędziwiatr ◽  
Radosław Kabut ◽  
Marta Bałajewicz-Nowak ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Demographic Data ◽  
Control Group ◽  
Healthy Controls ◽  
Microbiota Composition ◽  
Gastrointestinal Microbiota ◽  
The Difference ◽  
Generation Sequencing

Gut microbiome and colonic inflammation can be associated with the predisposition and progression of Parkinson’s disease (PD). The presented study aimed to compare gastrointestinal microbiota composition between patients diagnosed with PD and treated only with Levodopa to healthy controls. In this prospective study, patients were recruited in 1 academic hospital from July 2019 to July 2020. The detailed demographic data and medical history were collected using a set of questionnaires. Fecal samples were obtained from all participants. Next-Generation Sequencing was used to assess the microbiota composition. The endpoint was the difference in composition of the gut microbiota. In this study, we enrolled 27 hospitalized PD patients with well-controlled symptoms. The control group included 44 healthy subjects matched for age. Among PD patients, our results presented a higher abundance of Bacteroides phylum, class Corynebacteria among phylum Actinobacteria, class Deltaproteobacteria among phylum Proteobacteria, and genera such as Butyricimonas, Robinsoniella, and Flavonifractor. The species Akkermansia muciniphila, Eubacterium biforme, and Parabacteroides merdae were identified as more common in the gut microbiota of PD patients. In conclusion, the patients diagnosed with PD have significantly different gut microbiota profiles in comparison with healthy controls.

scholarly journals Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson’s disease in Upper Egypt: case-control study

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Hamdy N. El-Tallawy ◽  
Tahia H. Saleem ◽  
Wafaa M. Farghaly ◽  
Heba Mohamed Saad Eldien ◽  
Ashraf Khodaery ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Motor Symptoms ◽  
And Control ◽  
Non Motor Symptoms ◽  
Control Study

Abstract Background Parkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients. Results In a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8. Conclusion Genetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.

scholarly journals Glucocerebrosidase Activity is Reduced in Cryopreserved Parkinson’s Disease Patient Monocytes and Inversely Correlates with Motor Severity

2021 ◽  
pp. 1-9
Author(s):  
Laura P. Hughes ◽  
Marilia M.M. Pereira ◽  
Deborah A. Hammond ◽  
John B. Kwok ◽  
Glenda M. Halliday ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Rating Scale ◽  
Disease Patient ◽  
Motor Symptom ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Classical Monocytes

Background: Reduced activity of lysosomal glucocerebrosidase is found in brain tissue from Parkinson’s disease patients. Glucocerebrosidase is also highly expressed in peripheral blood monocytes where its activity is decreased in Parkinson’s disease patients, even in the absence of GBA mutation. Objective: To measure glucocerebrosidase activity in cryopreserved peripheral blood monocytes from 30 Parkinson’s disease patients and 30 matched controls and identify any clinical correlation with disease severity. Methods: Flow cytometry was used to measure lysosomal glucocerebrosidase activity in total, classical, intermediate, and non-classical monocytes. All participants underwent neurological examination and motor severity was assessed by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale. Results: Glucocerebrosidase activity was significantly reduced in the total and classical monocyte populations from the Parkinson’s disease patients compared to controls. GCase activity in classical monocytes was inversely correlated to motor symptom severity. Conclusion: Significant differences in monocyte glucocerebrosidase activity can be detected in Parkinson’s disease patients using cryopreserved mononuclear cells and monocyte GCase activity correlated with motor features of disease. Being able to use cryopreserved cells will facilitate the larger multi-site trials needed to validate monocyte GCase activity as a Parkinson’s disease biomarker.

scholarly journals Donepezil for mild cognitive impairment in Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyoungwon Baik ◽  
Seon Myeong Kim ◽  
Jin Ho Jung ◽  
Yang Hyun Lee ◽  
Seok Jong Chung ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Treatment Group ◽  
Outcome Measures ◽  
Rating Scale ◽  
Secondary Outcome ◽  
Control Group ◽  
Significant Difference

AbstractWe investigated the efficacy of donepezil for mild cognitive impairment in Parkinson’s disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson’s Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.

scholarly journals Integrated network analysis identifying potential novel drug candidates and targets for Parkinson's disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pusheng Quan ◽  
Kai Wang ◽  
Shi Yan ◽  
Shirong Wen ◽  
Chengqun Wei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Target ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Control Group ◽  
Drug Candidates ◽  
Novel Drug

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.

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