scholarly journals Cognitive Performance in Parkinson’s Disease in the Brain Health Registry

2019 ◽  
Vol 68 (3) ◽  
pp. 1029-1038 ◽  
Author(s):  
Brenna Cholerton ◽  
Michael W. Weiner ◽  
Rachel L. Nosheny ◽  
Kathleen L. Poston ◽  
R. Scott Mackin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Performance ◽  
Brain Health ◽  
Health Registry ◽  
The Brain

Gene expression analysis in modeling Parkinson’s disease

2020 ◽  
pp. 103-104
Author(s):  
М.М. Руденок ◽  
А.Х. Алиева ◽  
А.А. Колачева ◽  
М.В. Угрюмов ◽  
П.А. Сломинский ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Systemic Disease ◽  
Molecular Genetic ◽  
Presymptomatic Stage ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome ◽  
The Brain ◽  
Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

2020 ◽  
Vol 16 (1) ◽  
pp. 90-93
Author(s):  
Carmen E. Iriarte ◽  
Ian G. Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Candida Glabrata ◽  
High Sensitivity ◽  
Time Dependent ◽  
Colony Forming Units ◽  
Dependent Cell ◽  
The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

Analysis of Functional and Cognitive Impairment in Institutionalized Individuals with Movement Disorders

2019 ◽  
Vol 19 (7) ◽  
pp. 1022-1031 ◽  
Author(s):  
Paula D. Cebrián ◽  
Omar Cauli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Activities Of Daily Living ◽  
Cognitive Performance ◽  
Functional Impairment ◽  
Movement Disorders ◽  
Neurological Disorders ◽  
Daily Living ◽  
Severe Cognitive Impairment

Background: Many neurological disorders lead to institutionalization and can be accompanied in their advanced stages by functional impairment, and progressive loss of mobility, and cognitive alterations. Objective: We analyzed the relationship between functional impairment and cognitive performance and its related subdomains in individuals with Parkinson’s disease, Alzheimer’s disease accompanied by motor dysfunction, and with other neurological disorders characterized by both motor and cognitive problems. Methods: All participants lived in nursing homes (Valencia, Spain) and underwent cognitive evaluation with the Mini-Mental State Examination; functional assessment of independence in activities of daily living using the Barthel score and Katz index; and assessment of mobility with the elderly mobility scale. Results: The mean age of the subjects was 82.8 ± 0.6 years, 47% of the sample included individuals with Parkinson’s disease, and 48 % of the sample presented severe cognitive impairment. Direct significant relationships were found between the level of cognitive impairment and functional capacity (p < 0.01) and mobility (p < 0.05). Among the different domains, memory impairment was not associated with altered activities of daily living or mobility. The functional impairment and the risk of severe cognitive impairment were significantly (p<0.05) higher in female compared to male patients. Among comorbidities, overweight/obesity and diabetes were significantly (p < 0.05) associated with poor cognitive performance in those individuals with mild/moderate cognitive impairment. Conclusion: In institutionalized individuals with movement disorders there is an association between functional and cognitive impairment. Reduction of over-weight and proper control of diabetes may represent novel targets for improving cognitive function at such early stages.

scholarly journals Neuroinflammation and protein pathology in Parkinson’s disease dementia

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Antonina Kouli ◽  
Marta Camacho ◽  
Kieren Allinson ◽  
Caroline H. Williams-Gray
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Lymphocytes ◽  
Substantia Nigra ◽  
Amyloid Β ◽  
Brain Regions ◽  
Parkinson’S Disease Dementia ◽  
Activated Microglia ◽  
Cell Counts ◽  
The Brain

AbstractParkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.

Evaluation of Motor and Cognitive Performance in People with Parkinson’s Disease Using Instrumented Trail-Making Test

Gerontology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Ram kinker Mishra ◽  
Catherine Park ◽  
He Zhou ◽  
Bijan Najafi ◽  
T. Adam Thrasher
Keyword(s):  
Older Adults ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Performance ◽  
Pairwise Comparison ◽  
Walking Test ◽  
Cognitively Normal ◽  
Early Results ◽  
Trail Making ◽  
Changes Over Time

<b><i>Introduction:</i></b> Parkinson’s disease (PD) progressively impairs motor and cognitive performance. The current tools to detect decline in motor and cognitive functioning are often impractical for busy clinics and home settings. To address the gap, we designed an instrumented trail-making task (iTMT) based on a wearable sensor (worn on the shin) with interactive game-based software installed on a tablet. The iTMT test includes reaching to 5 indexed circles, a combination of numbers (1–3) and letters (A&amp;B) randomly positioned inside target circles, in a sequential order, which virtually appears on a screen kept in front of the participants, by rotating one’s ankle joint while standing and holding a chair for safety. By measuring time to complete iTMT task (iTMT time), iTMT enables quantifying cognitive-motor performance. <b><i>Purpose:</i></b> This study’s objective is to examine the feasibility of iTMT to detect early cognitive-motor decline in PDs. <b><i>Method:</i></b> Three groups of volunteers, including 14 cognitively normal (CN) older adults, 14 PDs, and 11 mild cognitive impaireds (MCI), were recruited. Participants completed MoCA, 20 m walking test, and 3 trials of iTMT. <b><i>Results:</i></b> All participants enabled to complete iTMT with &#x3c;3 min, indicating high feasibility. The average iTMT time for CN-Older, PD, and MCI participants were 20.9 ± 0.9 s, 32.3 ± 2.4 s, and 40.9 ± 4.5 s, respectively. After adjusting for age and education level, pairwise comparison suggested large effect sizes for iTMT between CN-older versus PD (Cohen’s <i>d</i> = 1.7, <i>p</i> = 0.024) and CN-older versus MCI (<i>d</i> = 1.57, <i>p</i> &#x3c; 0.01). Significant correlations were observed when comparing iTMT time with the gait speed (<i>r</i> = −0.4, <i>p</i> = 0.011) and MoCA score (<i>r</i> = −0.56, <i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> This study demonstrated the feasibility and early results supporting the potential application of iTMT to determine cognitive-motor and distinguishing individuals with MCI and PD from CN-older adults. Future studies are warranted to test the ability of iTMT to track its subtle changes over time.

scholarly journals Evading the Immune System: Immune Modulation and Immune Matching in Cell Replacement Therapies for Parkinson’s Disease

2021 ◽  
pp. 1-6
Author(s):  
Asuka Morizane ◽  
Jun Takahashi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Immune Modulation ◽  
Autologous Transplantation ◽  
Human Leukocyte ◽  
Allogeneic Transplantation ◽  
Leukocyte Antigen ◽  
The Brain

Stem cell-based therapies for Parkinson’s disease are now being applied clinically. Notably, studies have shown that controlling the graft-induced immune response improves the results. In this mini-review, we concisely summarize current approaches used for this control. We focus on four modes of stem cell-based therapies: autologous transplantation, allogeneic transplantation with human leukocyte antigen-matching and allogeneic transplantation without, and finally the application of “universal” pluripotent stem cells. We also discuss immuno-suppressive treatments and the monitoring of immune reactions in the brain.

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