scholarly journals Genetic Analysis and Literature Review of SNCA Variants in Parkinson's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Yi Guo ◽  
Yan Sun ◽  
Zhi Song ◽  
Wen Zheng ◽  
Wei Xiong ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Literature Review ◽  
Cognitive Decline ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Han Chinese ◽  
Control Group ◽  
Familial Form ◽  
Significant Difference

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder. Aging, environmental factors, and genetics are considered as risk factors. The alpha-synuclein gene (SNCA), the first pathogenic gene identified in a familial form of PD, was indisputably involved as a heritable component for familial and sporadic PD. In this study, whole-exome sequencing and Sanger sequencing were performed to evaluate the association between the SNCA gene variants and PD. The genetic data of 438 clinically diagnosed patients with PD and 543 matched control populations of the Han Chinese were analyzed. The literature review of SNCA variants for 231 cases reported in 89 articles was extracted from the PubMed and the Movement Disorder Society Genetic mutation database. No potentially causative variant(s) in the SNCA gene, excepting two single-nucleotide nonsynonymous variants c.158C>T (p.A53V, rs542171324) and c.349C>T (p.P117S, rs145138372), were detected. There was no statistically significant difference in the genotypic or allelic frequencies for either variant between the PD group and the control group (all P > 0.05). No copy number variants of the SNCA gene were detected. The results of this study suggest that the variants in the exons of the SNCA gene may have less or no role in the development of PD in the Han Chinese populations. The literature review suggests that psychiatric signs and cognitive decline/dementia were more common among patients with SNCA duplication or triplication (psychiatric signs: χ2 = 7.892, P = 0.005; cognitive decline/dementia: χ2 = 8.991, P = 0.003).

Plasma exosomal alpha-synuclein in inherited forms of Parkinson’s disease

2020 ◽  
pp. 99-100
Author(s):  
Д.Г. Кулабухова ◽  
А.К. Емельянов ◽  
К.А. Сенкевич ◽  
Е.В. Грачева ◽  
И.В. Милюхина ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Blood Plasma ◽  
Peripheral Blood ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Significant Difference ◽  
Peripheral Blood Plasma

Предполагается, что экзосомы (микровезикулы размером 40-100 нм) могут играть ключевую роль в транспорте патогенных форм альфа-синуклеина при болезни Паркинсона (БП). В настоящем исследовании проведена оценка влияния мутаций в генах GBA и LRRK2 на уровень альфа-синуклеина экзосом плазмы крови. Показано, что мутации в генах GBA и LRRK2 не влияют на уровень альфа-синуклеина экзосом плазмы крови. Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder. Alpha-synuclein misfolding and aggregation resulting in neurototoxicity is a hallmark of PD. Exosomes (extrcellular vesicles 40-100 nm in size) can play a key role in the transport of pathogenic forms of alpha-synuclein. The aim of our work is to evaluate an effect of GBA and LRRK2 mutations on alpha-synuclein level in exosomes derived from peripheral blood plasma. No significant difference was found for exosomal alpha-synuclein levels patients with sporadic, GBA- and LRRK2- associated PD, PD with dementia compared to controls. Our results indicate that mutations in the LRRK2 and GBA genes do not influence on plasma exosomal alpha-synuclein level.

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 Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 314
Author(s):  
Aida Arroyo-Ferrer ◽  
Francisco José Sánchez-Cuesta ◽  
Yeray González-Zamorano ◽  
María Dolores del Castillo ◽  
Carolina Sastre-Barrios ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Therapy ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Cognitive Rehabilitation ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Motor Symptoms ◽  
The Impact

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

The Incidence of Parkinson's Disease: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 46 (4) ◽  
pp. 292-300 ◽  
Author(s):  
Lauren Hirsch ◽  
Nathalie Jette ◽  
Alexandra Frolkis ◽  
Thomas Steeves ◽  
Tamara Pringsheim
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Meta Analysis ◽  
Age Groups ◽  
Significant Heterogeneity ◽  
International Studies ◽  
Significant Difference ◽  
And Gender

Background: Parkinson's disease (PD) is a common neurodegenerative disorder. Epidemiological studies on the incidence of PD are important to better understand the risk factors for PD and determine the condition's natural history. Objective: This systematic review and meta-analysis examine the incidence of PD and its variation by age and gender. Methods: We searched MEDLINE and EMBASE for epidemiologic studies of PD from 2001 to 2014, as a previously published systematic review included studies published until 2001. Data were analyzed separately for age group and gender, and meta-regression was used to determine whether a significant difference was present between groups. Results: Twenty-seven studies were included in the analysis. Meta-analysis of international studies showed rising incidence with age in both men and women. Significant heterogeneity was observed in the 80+ group, which may be explained by methodological differences between studies. While males had a higher incidence of PD in all age groups, this difference was only statistically significant for those in the age range 60-69 and 70-79 (p < 0.05). Conclusion: PD incidence generally increases with age, although it may stabilize in those who are 80+.

scholarly journals Alpha-Synuclein Induced Immune Cells Activation and Associated Therapy in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Ruichen Su ◽  
Tian Zhou
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Immune Cells ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Autoimmune Response ◽  
T Helper ◽  
Helper Type

Parkinson’s disease (PD) is a neurodegenerative disorder closely related to immunity. An important aspect of the pathogenesis of PD is the interaction between α-synuclein and a series of immune cells. Studies have shown that accumulation of α-synuclein can induce an autoimmune response that accelerates the progression of PD. This study discusses the mechanisms underlying the interaction between α-synuclein and the immune system. During the development of PD, abnormally accumulated α-synuclein becomes an autoimmune antigen that binds to Toll-like receptors (TLRs) that activate microglia, which differentiate into the microglia type 1 (M1) subtype. The microglia activate intracellular inflammatory pathways, induce the release of proinflammatory cytokines, and promote the differentiation of cluster of differentiation 4 + (CD4 +) T cells into proinflammatory T helper type 1 (Th1) and T helper type 17 (Th17) subtypes. Given the important role of α-synuclein in the immune system of the patients with PD, identifying potential targets of immunotherapy related to α-synuclein is critical for slowing disease progression. An enhanced understanding of immune-associated mechanisms in PD can guide the development of associated therapeutic strategies in the future.

Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid in Parkinson’s disease and atypical parkinsonian syndromes

2021 ◽  
Author(s):  
Michaela Kaiserova ◽  
Monika Chudackova ◽  
Hana Prikrylova Vranova ◽  
Katerina Mensikova ◽  
Anetta Kastelikova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Statistical Significance ◽  
Corticobasal Degeneration ◽  
Control Group ◽  
Csf Biomarkers ◽  
Parkinsonian Syndromes ◽  
Significant Difference ◽  
Hydroxyindoleacetic Acid

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal degeneration (CBD) patients, and 31 controls. We also compared the values in depressed and non-depressed patients. Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 µg/l, in MSA 13.6 µg/l vs. 24.3 µg/l in controls; P=0.0008 in PD, P=0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBD compared to the control group (median in PSP 22.7 µg/l, in CBD 18.7 µg/l vs. 24.3 µg/l in controls; P= 1 in both PSP and CBD). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, P<0.0001). Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD, however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD, MSA) than in tauopathies (PSP, CBS).

scholarly journals Palmitate and Stearate are Increased in the Plasma in a 6-OHDA Model of Parkinson’s Disease

Metabolites ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 31 ◽  
Author(s):  
Anuri Shah ◽  
Pei Han ◽  
Mung-Yee Wong ◽  
Raymond Chang ◽  
Cristina Legido-Quigley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Neurodegenerative Disorder ◽  
Motor Dysfunction ◽  
Substantia Nigra Pars Compacta ◽  
Control Group ◽  
Sprague Dawley ◽  
Curative Therapy

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, without any widely available curative therapy. Metabolomics is a powerful tool which can be used to identify unexpected pathway-related disease progression and pathophysiological mechanisms. In this study, metabolomics in brain, plasma and liver was investigated in an experimental PD model, to discover small molecules that are associated with dopaminergic cell loss. Methods: Sprague Dawley (SD) rats were injected unilaterally with 6-hydroxydopamine (6-OHDA) or saline for the vehicle control group into the medial forebrain bundle (MFB) to induce loss of dopaminergic neurons in the substantia nigra pars compacta. Plasma, midbrain and liver samples were collected for metabolic profiling. Multivariate and univariate analyses revealed metabolites that were altered in the PD group. Results: In plasma, palmitic acid (q = 3.72 × 10−2, FC = 1.81) and stearic acid (q = 3.84 × 10−2, FC = 2.15), were found to be increased in the PD group. Palmitic acid (q = 3.5 × 10−2) and stearic acid (q = 2.7 × 10−2) correlated with test scores indicative of motor dysfunction. Monopalmitin (q = 4.8 × 10−2, FC = −11.7), monostearin (q = 3.72 × 10−2, FC = −15.1) and myo-inositol (q = 3.81 × 10−2, FC = −3.32), were reduced in the midbrain. The liver did not have altered levels of these molecules. Conclusion: Our results show that saturated free fatty acids, their monoglycerides and myo-inositol metabolism in the midbrain and enteric circulation are associated with 6-OHDA-induced PD pathology.

scholarly journals LINEAR ASSESSMENT OF CEREBRAL AUTOREGULATION IN IDIOPATHIC PARKINSON'S DISEASE

2016 ◽  
Vol 8 (2) ◽  
pp. 14
Author(s):  
Chuang-chien Chiu ◽  
Ken Ying-kai Liao ◽  
Shoou-jeng Yeh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebral Autoregulation ◽  
System Analysis ◽  
Cerebral Blood Flow Velocity ◽  
Function Analysis ◽  
Control Group ◽  
Power Spectral ◽  
Significant Difference ◽  
Density Analysis

<p class="lead">Parkinson’s disease cases have been on the rise in the recent years, which promoted several different researches into the disorder. However, there hasn’t much research been done in the non-motor aspects of the disease. This study aims to improve the understanding of one of the non-motor symptoms of Parkinson’s disease. Specifically, this research aims to further understand cerebral autoregulation in patients with Parkinson’s disease. In order to achieve this aim, 25 subjects were recruited, with 11 healthy controls and 14 patients with Parkinson’s disease. The continuous blood pressure and continuous cerebral blood flow velocity of all subjects were recorded and processed while the subjects were at rest, tilt-up, and during hyperventilation. Linear signal and system analysis techniques were applied such as the power spectral density analysis and cross-correlation function analysis. Results showed that patients with Parkinson’s disease did not show a significant difference from the control group while at rest and after tilt-up. However, there was a significant difference between the groups during hyperventilation. The results obtained in this study suggested that the metabolic regulatory pathway for cerebral autoregulation is impaired in patients with Parkinson’s disease.</p>

scholarly journals miR-185 and SEPT5 Genes May Contribute to Parkinson’s Disease Pathophysiology

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Arman Rahimmi ◽  
Ilaria Peluso ◽  
Aref Rajabi ◽  
Kambiz Hassanzadeh
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Chromosomal Location ◽  
Gene Expression Pattern ◽  
Control Group ◽  
Significant Difference

There are still unknown mechanisms involved in the development of Parkinson’s disease (PD), which elucidating them can assist in developing efficient therapies. Recently, studies showed that genes located on the human chromosomal location 22q11.2 might be involved in the development of PD. Therefore, the present study was designed to evaluate the role of two genes located on the chromosomal location (miR-185 and SEPT5), which were the most probable candidates based on our bibliography. In vivo and in vitro models of PD were developed using male Wistar rats and SHSY-5Y cell line, respectively. The expression levels of miR-185, SEPT5, LRRK2, and PARK2 genes were measured at a mRNA level in dopaminergic areas of rats’ brains and SHSY-5Y cells using the SYBR Green Real-Time PCR Method. Additionally, the effect of inhibition on the genes or their products on cell viability and gene expression pattern in SHSY-5Y cells was investigated. The level of miR-185 gene expression was significantly decreased in the substantia nigra (SN) and striatum (ST) of the rotenone-treated group (control group) compared to the healthy normal group (P<0.05). In addition, there was a significant difference in the expression of SEPT5 gene (P<0.05) in the substantia nigra between two studied groups. The results of an in vitro study showed no significant change in the expression of the genes; however, the inhibition on miR-185 gene expression led to the increase in LRRK2 gene expression in SHSY-5Y cells. The inhibition on LRRK2 protein also decreased the cellular toxicity effect of rotenone on SHSY-5Y cells. The results suggested the protective role of miR-185 gene in preventing the development of PD.

CO-MORBIDITY BURDEN IN PARKINSON'S DISEASE AND MATCHED CONTROLS

2015 ◽  
Vol 86 (11) ◽  
pp. e4.86-e4
Author(s):  
Hannah Goddard ◽  
Angus Macleod ◽  
Carl Counsell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Predictive Ability ◽  
Morbidity Burden ◽  
Co Morbidity ◽  
Significant Difference ◽  
Morbidity Index

BackgroundIdiopathic Parkinson's disease (PD) is a common, disabling, neurodegenerative disorder. The overall co-morbidity burden associated with PD is unclear, but may be important to adjust for when predicting prognosis or comparing cases and controls.Aims ▸ To determine how best to assess overall co-morbidity in PD▸ To compare PD co-morbidity burden to that of age- and sex-matched controlsMethodsData from an incident, community-based cohort of 205 patients with PD and 148 age-, sex- and GP-matched controls (the PINE study) were used. The intra- and inter-rater reliability and mortality predictive ability of three co-morbidity scales (the Charlson Co-Morbidity Index, the Cumulative Illness Rating Scale and a disease count) were evaluated. The co-morbidity burden of cases and controls was compared at baseline and over 5 years of follow-up.Results and conclusionsThe Charlson Co-Morbidity Index was more reliable for use in PD and was the only scale that was independently predictive of mortality (hazard ratio=1.20, [95% CI 1.07–1.34]). There was no significant difference between cases and controls at baseline (p=0.20). Charlson Co-Morbidity Index scores increased over time. This increase was greater in patients with PD than controls and greater in patients and controls who died earlier.

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