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HSP90 and Its Novel Co-Chaperones, SGT1 and CHP-1, in Brain of Patients with Parkinson's Disease and Dementia with Lewy Bodies.
Bohush, A, Niewiadomska, G, Weis, S, Filipek, A
Journal of Parkinson's disease. 2019;(1):97-107
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Abstract
BACKGROUND Parkinson's disease (PD) is a neurodegenerative disorder characterized by the presence of inclusions known as Lewy bodies in some brain regions. Lewy bodies consist of α-synuclein and many other proteins including chaperones. OBJECTIVE To learn more about the role of chaperone complexes in PD and a related disorder, i.e., dementia with Lewy bodies (DLB), in this work we analyzed the expression of HSP90 and its two quite recently identified co-chaperones, SGT1 and CHP-1, in selected brain regions from patients suffering from these diseases. METHODS To fulfill the aim of our study we used human material and applied immunohistochemistry, Western blot analysis and real time/quantitative PCR (RT-qPCR). RESULTS We have found that HSP90 mRNA level is higher in the temporal cortex of PD and in frontal cortex of DLB brains, even though level of protein does not change significantly. The mRNA level of SGT1 is higher in the frontal and temporal cortex of PD and in substantia nigra of DLB brains while no significant changes in the level of protein were noticed. Similarly, the mRNA level of CHP-1 was found to be higher in the frontal and temporal cortex of PD and in all examined regions i.e. substantia nigra, frontal and temporal cortex of DLB brains. In the case of CHP-1 the protein level was found to be higher in frontal cortex of PD and in all examined areas of DLB patients. CONCLUSIONS Our data indicate that the level of HSP90, SGT1 and CHP-1 is upregulated in the majority of cases of PD and DLB, which suggests that the examined proteins might be involved in these pathologies.
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The effects of acupuncture and electroacupuncture on Parkinson's disease: Current status and future perspectives for molecular mechanisms.
Tamtaji, OR, Naderi Taheri, M, Notghi, F, Alipoor, R, Bouzari, R, Asemi, Z
Journal of cellular biochemistry. 2019;(8):12156-12166
Abstract
Among the progressive neurodegenerative disorders, Parkinson's disease (PD) is the second most common. Different factors have critical role in pathophysiology of PD such as apoptosis pathways, inflammatory cytokines, oxidative stress, and neurotransmitters and its receptors abnormalities. Acupuncture and electroacupuncture were considered as nondrug therapies for PD. Although numerous studies has been conducted for assessing the mechanism underlying electroacupuncture and acupuncture, various principal aspects of these treatment procedures remain not well-known. There have also been few investigations on the molecular mechanism of acupuncture and electroacupuncture therapy effects in PD. This review evaluates the effects of electroacupuncture and acupuncture on the molecular mechanism in PD.
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Impacts of dance on cognition, psychological symptoms and quality of life in Parkinson's disease.
Kalyani, HHN, Sullivan, KA, Moyle, G, Brauer, S, Jeffrey, ER, Kerr, GK
NeuroRehabilitation. 2019;(2):273-283
Abstract
BACKGROUND While dance may improve motor features in Parkinson's disease (PD), it is not yet clear if the benefits extend to non-motor features. OBJECTIVE To determine whether dance classes based on Dance for PD®, improve cognition, psychological symptoms and Quality of Life (QoL) in PD. METHODS Participants were allocated to a Dance Group (DG; n = 17) or Control Group (CG: n = 16). Participants had early-stage PD (Hoehn & Yahr: DG = 1.6±0.7, CG = 1.5±0.8) with no cognitive impairment (Addenbrooke's score: DG = 93.2±3.6, CG = 92.6±4.3). The DG undertook a one-hour class, twice weekly for 12 weeks, while the CG had treatment as usual. Both groups were assessed for disease severity (MDS-UPDRS), cognition (NIH Toolbox® cognition battery, Trail Making Test), psychological symptoms (Hospital Anxiety and Depression Scale, MDS-UPDRS-I) and QoL (PDQ-39, MDS-UPDRS-II). RESULTS Group comparison of pre-post change scores showed that selected cognitive skills (executive function and episodic memory), psychological symptoms (anxiety and depression) as well as QoL (PDQ-39 summary index) were significantly improved by the intervention (DG > CG, p's < 0.05, Cohen's d > 0.8). DISCUSSIONS AND CONCLUSION Dance classes had a clear benefit on psychological symptoms, QoL and a limited cognitive benefit. Follow-up assessment is required to confirm the durability of these effects.
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Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson's Disease.
Hertel, J, Harms, AC, Heinken, A, Baldini, F, Thinnes, CC, Glaab, E, Vasco, DA, Pietzner, M, Stewart, ID, Wareham, NJ, et al
Cell reports. 2019;(7):1767-1777.e8
Abstract
Parkinson's disease (PD) exhibits systemic effects on the human metabolism, with emerging roles for the gut microbiome. Here, we integrate longitudinal metabolome data from 30 drug-naive, de novo PD patients and 30 matched controls with constraint-based modeling of gut microbial communities derived from an independent, drug-naive PD cohort, and prospective data from the general population. Our key results are (1) longitudinal trajectory of metabolites associated with the interconversion of methionine and cysteine via cystathionine differed between PD patients and controls; (2) dopaminergic medication showed strong lipidomic signatures; (3) taurine-conjugated bile acids correlated with the severity of motor symptoms, while low levels of sulfated taurolithocholate were associated with PD incidence in the general population; and (4) computational modeling predicted changes in sulfur metabolism, driven by A. muciniphila and B. wadsworthia, which is consistent with the changed metabolome. The multi-omics integration reveals PD-specific patterns in microbial-host sulfur co-metabolism that may contribute to PD severity.
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Implications of Vitamin D in Multiple Sclerosis and Other Neurodegenerative Processes: Bibliometric Analysis and Systematic Review.
Caballero-Villarraso, J, Jiménez-Jiménez, MJ, Escribano, BM, Agüera, E, Santamaría, A, Túnez, I
CNS & neurological disorders drug targets. 2019;(6):478-490
Abstract
In recent years, numerous investigations focused on the pleiotropic actions of vitamin D have been carried out. These actions include the participation of this molecule in neurophysiological and neuropathological processes. As a consequence, abundant scientific literature on the role of this vitamin in neurodegenerative entities has emerged, even concerning clinical studies. To identify the level of scientific evidence concerning the relation between vitamin D and neurodegenerative diseases, from a quantitative and qualitative perspective. To describe, by means of a bibliometric analysis, the scientific production and its evolution through time in quantitative terms, regarding the implications of vitamin D in neurodegeneration. To analyse and present the degree of evidence in the aforementioned field of study, a systematic review of the literature focused on the most prevalent neurodegenerative diseases was carried out. We retrieved 848 articles in the bibliometric analysis, the majority of which were dated between the years 2010-2017. The most studied metabolite was the 25(OH)D3 and the most cited disease was multiple sclerosis. In the systematic review, we found studies about Alzheimer's and Parkinson's diseases and again, about multiple sclerosis prominently (in number and quality), with 12 randomised double-blind clinical trials. The research about vitamin D and its relations with neurodegenerative diseases shows a growing evolution over the last decade. More studies are needed to find correlations between the clinical severity of these diseases and the specific status of vitamin D and the genotypes related with them, which seems to be a future trend.
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Switching on Endogenous Metal Binding Proteins in Parkinson's Disease.
McLeary, FA, Rcom-H'cheo-Gauthier, AN, Goulding, M, Radford, RAW, Okita, Y, Faller, P, Chung, RS, Pountney, DL
Cells. 2019;(2)
Abstract
The formation of cytotoxic intracellular protein aggregates is a pathological signature of multiple neurodegenerative diseases. The principle aggregating protein in Parkinson's disease (PD) and atypical Parkinson's diseases is α-synuclein (α-syn), which occurs in neural cytoplasmic inclusions. Several factors have been found to trigger α-syn aggregation, including raised calcium, iron, and copper. Transcriptional inducers have been explored to upregulate expression of endogenous metal-binding proteins as a potential neuroprotective strategy. The vitamin-D analogue, calcipotriol, induced increased expression of the neuronal vitamin D-dependent calcium-binding protein, calbindin-D28k, and this significantly decreased the occurrence of α-syn aggregates in cells with transiently raised intracellular free Ca, thereby increasing viability. More recently, the induction of endogenous expression of the Zn and Cu binding protein, metallothionein, by the glucocorticoid analogue, dexamethasone, gave a specific reduction in Cu-dependent α-syn aggregates. Fe accumulation has long been associated with PD. Intracellularly, Fe is regulated by interactions between the Fe storage protein ferritin and Fe transporters, such as poly(C)-binding protein 1. Analysis of the transcriptional regulation of Fe binding proteins may reveal potential inducers that could modulate Fe homoeostasis in disease. The current review highlights recent studies that suggest that transcriptional inducers may have potential as novel mechanism-based drugs against metal overload in PD.
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Dopamine Cytotoxicity on SH-SY5Y Cells: Involvement of α-Synuclein and Relevance in the Neurodegeneration of Sporadic Parkinson's Disease.
Ganguly, U, Ganguly, A, Sen, O, Ganguly, G, Cappai, R, Sahoo, A, Chakrabarti, S
Neurotoxicity research. 2019;(4):898-907
Abstract
The cytotoxicity of dopamine on cultured cells of neural origin has been used as a tool to explore the mechanisms of dopaminergic neurodegeneration in Parkinson's disease. In the current study, we have shown that dopamine induces a dose-dependent (10-40 μM) and time-dependent (up to 96 h) loss of cell viability associated with mitochondrial dysfunction and increased intra-cellular accumulation of α-synuclein in cultured SH-SY5Y cells. Dopamine-induced mitochondrial dysfunction and the loss of cell viability under our experimental conditions could be prevented by cyclosporine, a blocker of mitochondrial permeability transition pore, as well as the antioxidant N-acetylcysteine. Interestingly, the dopamine effects on cell viability and mitochondrial functions were significantly prevented by knocking down α-synuclein expression by specific siRNA. Our results suggest that dopamine cytotoxicity is mediated by α-synuclein acting on the mitochondria and impairing its bioenergetic functions.
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Role of Dietary Supplements in the Management of Parkinson's Disease.
Ciulla, M, Marinelli, L, Cacciatore, I, Stefano, AD
Biomolecules. 2019;(7)
Abstract
The use of food supplements or functional food has significantly increased in the past decades, especially to compensate both the modern lifestyle and the food shortages of the industrialized countries. Despite food supplements are habitually intended to correct nutritional deficiencies or to support specific physiological functions, they are often combined with common drug therapies to improve the patient's health and/or mitigate the symptoms of many chronic diseases such as cardiovascular diseases, cystic fibrosis, cancer, liver and gastrointestinal diseases. In recent years, increased attentions are given to the patient's diet, and the use of food supplements and functional food rich in vitamins and antioxidants plays a very important role in the treatment and prevention of neurodegenerative diseases such as Parkinson's disease (PD). Natural compounds, phytochemicals, vitamins, and minerals can prevent, delay, or alleviate the clinical symptoms of PD in contrast to some of the main physiopathological mechanisms involved in the development of the disease, like oxidative stress, free radical formation, and neuroinflammation. The purpose of this review is to collect scientific evidences which support the use of specific biomolecules and biogenic elements commonly found in food supplements or functional food to improve the clinical framework of patients with PD.
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Falls Self-Management Interventions for People with Parkinson's Disease: A Systematic Review.
Owen, CL, Ibrahim, K, Dennison, L, Roberts, HC
Journal of Parkinson's disease. 2019;(2):283-299
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Abstract
BACKGROUND Falls are common in Parkinson's disease (PD). Increased involvement of people with Parkinson's (PwP) in their care has been associated with enhanced satisfaction. Self-management programmes in other long-term conditions (LTCs) have led to improvements in physical and psychological outcomes. These have been more effective when targeted toward a specific behavior. OBJECTIVE This paper aimed to identify and review falls self-management interventions for PwP. METHODS A systematic review was conducted. Electronic databases were searched in June 2018. Primary research studies (any design) reporting the delivery of falls self-management interventions to PwP were included. Data was extracted from each article and synthesised narratively. RESULTS Six articles were identified, relating to five different self-management interventions. All described a self-management intervention delivered alongside physiotherapy. Intervention delivery was through either group discussion (n = 3) or falls booklets (n = 3). Interventions were often incompletely described; the most common components were information about the condition, training/ rehearsal for psychological strategies and lifestyle advice and support. Arising from the design of articles included the effects of self-management and physiotherapy could not be separated. Three articles measured falls, only one led to a reduction. Four articles measured quality of life, only one led to improvement. No articles assessed skill acquisition or adherence to the self-management intervention. CONCLUSIONS Few falls self-management interventions for PwP have been evaluated and reported. The components of an effective intervention remain unclear. Given the benefits of self-management interventions in other LTCs, it is important that falls self-management interventions are developed and evaluated to support PwP.
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Quantifying physical activity in early Parkinson disease using a commercial activity monitor.
Pradhan, S, Kelly, VE
Parkinsonism & related disorders. 2019;:171-175
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Abstract
INTRODUCTION Physical inactivity in Parkinson disease (PD) has an impact on motor and non-motor symptoms of the disease. It is unclear whether this decline in physical activity occurs early in the disease, in addition to any decline due to aging, and whether commercial activity monitors can be used to self-monitor physical activity levels in this population. OBJECTIVE To compare the quantity and intensity of physical activity (PA), as measured by commercial activity monitors, in people with mild PD and healthy older adults (HOA). A secondary objective was to assess adherence and user experience with wearing the activity monitoring device. METHODS An observational descriptive study design examined PA levels over a 14-day period using commercially-available activity monitors (Fitbit Charge HR). RESULTS Individuals with PD (n = 30) and HOA (n = 30) both demonstrated high adherence with wear time (PD = 13.8 [0.5] days, HOA = 13.9 [0.4] days, p = 0.55). People with PD took fewer steps per day than HOA (PD = 6416.9 (2795.5), HOA = 11441.3 (3932.1), p < 0.001). Compared to HOA, individuals with PD spent fewer minutes per day engaged in moderate to vigorous intensity activity (PD = 33.0 (22.5), HOA = 72.0(37.3), p < 0.001) and more minutes per day sedentary (PD = 803.74 (154.9), HOA = 578.26 (103.7), p < 0.001). Both groups reported that ease of use and satisfaction with the activity monitor were high. CONCLUSIONS People with mild PD demonstrated reduced quantity and intensity of PA compared to HOA. Both the PD and the HOA groups had good adherence wearing a commercial activity monitor that provided feedback regarding activity levels.