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https://www.readbyqxmd.com/read/28918091/opposed-effects-of-dityrosine-formation-in-soluble-and-aggregated-%C3%AE-synuclein-on-fibril-growth
#1
Michael M Wördehoff, Hamed Shaykhalishahi, Luca Groß, Lothar Gremer, Matthias Stoldt, Alexander K Buell, Dieter Willbold, Wolfgang Hoyer
Parkinson's disease (PD) is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY)-crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from PD patients. Here we report that α-syn is highly susceptible to UV-induced DiY formation...
September 13, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28917260/roles-of-sigma-1-receptors-on-mitochondrial-functions-relevant-to-neurodegenerative-diseases
#2
REVIEW
Tzu-Yu Weng, Shang-Yi Anne Tsai, Tsung-Ping Su
The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. At the MAM, the Sig-1R is known to play a role in regulating the Ca(2+) signaling between ER and mitochondria and in maintaining the structural integrity of the MAM. The MAM serves as bridges between ER and mitochondria regulating multiple functions such as Ca(2+) transfer, energy exchange, lipid synthesis and transports, and protein folding that are pivotal to cell survival and defense...
September 16, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28916538/analysis-of-blood-based-gene-expression-in-idiopathic-parkinson-disease
#3
Ron Shamir, Christine Klein, David Amar, Eva-Juliane Vollstedt, Michael Bonin, Marija Usenovic, Yvette C Wong, Ales Maver, Sven Poths, Hershel Safer, Jean-Christophe Corvol, Suzanne Lesage, Ofer Lavi, Günther Deuschl, Gregor Kuhlenbaeumer, Heike Pawlack, Igor Ulitsky, Meike Kasten, Olaf Riess, Alexis Brice, Borut Peterlin, Dimitri Krainc
OBJECTIVE: To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). METHODS: Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature...
September 15, 2017: Neurology
https://www.readbyqxmd.com/read/28914791/quercetin-attenuates-manganese-induced-neuroinflammation-by-alleviating-oxidative-stress-through-regulation-of-apoptosis-inos-nf-%C3%AE%C2%BAb-and-ho-1-nrf2-pathways
#4
Entaz Bahar, Ji-Ye Kim, Hyonok Yoon
Manganese (Mn) is an essential trace element required for the development of human body and acts as an enzyme co-factor or activator for various reactions of metabolism. While essential in trace amounts, excessive Mn exposure can result in toxic accumulations in human brain tissue and resulting extrapyramidal symptoms called manganism similar to idiopathic Parkinson's disease (PD). Quercetin (QCT) has been demonstrated to play an important role in altering the progression of neurodegenerative diseases by protecting against oxidative stress...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28902670/neuroprotective-effects-of-coenzyme-q10-on-paraquat-induced-parkinson-s-disease-in-experimental-animals
#5
Hanan Naeim Attia, Yousreya Aly Maklad
Parkinson's disease (PD) affects ∼1-2% of the elderly population. Development of a neuroprotective therapy that may be initiated early in the course of the disease to retard/prevent disease progression is highly desirable. This study aimed to investigate prophylactic treatment with coenzyme Q10 (CoQ10) before paraquat (PQ) exposure, a herbicide known to increase the risk for PD, to attain neuroprotection. In addition, therapeutic intervention with CoQ10 in mice already exposed to PQ (24 h) might halt ongoing neurodegeneration and behavioural deterioration...
September 11, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28901595/movement-disorders-in-genetically-confirmed-mitochondrial-disease-and-the-putative-role-of-the-cerebellum
#6
Sebastian R Schreglmann, Franz Riederer, Marian Galovic, Christos Ganos, Georg Kägi, Daniel Waldvogel, Zane Jaunmuktane, Andre Schaller, Ute Hidding, Ernst Krasemann, Lars Michels, Christian R Baumann, Kailash Bhatia, Hans H Jung
BACKGROUND: Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce. OBJECTIVE: The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders. METHODS: In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video-documented movement disorders was assessed...
September 13, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28899515/the-water-extract-of-liuwei-dihuang-possesses-multi-protective-properties-on-neurons-and-muscle-tissue-against-deficiency-of-survival-motor-neuron-protein
#7
Yu-Ting Tseng, Yuh-Jyh Jong, Wei-Fang Liang, Fang-Rong Chang, Yi-Ching Lo
BACKGROUND: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28883016/mitochondrial-dynamics-in-parkinson-s-disease-a-role-for-%C3%AE-synuclein
#8
REVIEW
Victorio M Pozo Devoto, Tomas L Falzone
The distinctive pathological hallmarks of Parkinson's disease are the progressive death of dopaminergic neurons and the intracellular accumulation of Lewy bodies enriched in α-synuclein protein. Several lines of evidence from the study of sporadic, familial and pharmacologically induced forms of human Parkinson's disease also suggest that mitochondrial dysfunction plays an important role in disease progression. Although many functions have been proposed for α-synuclein, emerging data from human and animal models of Parkinson's disease highlight a role for α-synuclein in the control of neuronal mitochondrial dynamics...
September 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28882997/dopamine-oxidation-mediates-mitochondrial-and-lysosomal-dysfunction-in-parkinson-s-disease
#9
Lena F Burbulla, Pingping Song, Joseph R Mazzulli, Enrico Zampese, Yvette C Wong, Sohee Jeon, David P Santos, Judith Blanz, Carolin D Obermaier, Chelsee Strojny, Jeffrey N Savas, Evangelos Kiskinis, Xiaoxi Zhuang, Rejko Krüger, D James Surmeier, Dimitri Krainc
Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation, ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction and α-synuclein accumulation...
September 7, 2017: Science
https://www.readbyqxmd.com/read/28880525/mitoneet-cisd1-knockout-mice-show-signs-of-striatal-mitochondrial-dysfunction-and-a-parkinson-s-disease-phenotype
#10
Werner J Geldenhuys, Stanley A Benkovic, Li Lin, Heather M Yonutas, Samuel D Crish, Patrick G Sullivan, Altaf S Darvesh, Candice M Brown, Jason Richardson
Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson's disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron-sulfur containing protein which regulates mitochondrial bioenergetics, results in mitochondrial dysfunction and loss of striatal dopamine and tyrosine hydroxylase. Mitochondria isolated from mice lacking mitoNEET were dysfunctional as revealed by elevated reactive oxygen species (ROS) and reduced capacity to produce ATP...
September 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28877188/mitochondrial-superclusters-influence-age-of-onset-of-parkinson-s-disease-in-a-gender-specific-manner-in-the-cypriot-population-a-case-control-study
#11
Andrea Georgiou, Christiana A Demetriou, Alexandros Heraclides, Yiolanda P Christou, Eleni Leonidou, Panayiotis Loukaides, Elena Yiasoumi, Dimitris Panagiotou, Panayiotis Manoli, Pippa Thomson, Maria A Loizidou, Andreas Hadjisavvas, Eleni Zamba-Papanicolaou
BACKGROUND: Despite evidence supporting an involvement of mitochondrial dysfunction in the pathogenesis of some neurodegenerative disorders, there are inconsistent findings concerning mitochondrial haplogroups and their association to neurodegenerative disorders, including idiopathic Parkinson's disease (PD). METHODS: To test this hypothesis for the Greek-Cypriot population, a cohort of 230 PD patients and 457 healthy matched controls were recruited. Mitochondrial haplogroup distributions for cases and controls were determined...
2017: PloS One
https://www.readbyqxmd.com/read/28874699/metal-concentrations-and-distributions-in-the-human-olfactory-bulb-in-parkinson-s-disease
#12
Bronwen Gardner, Birger V Dieriks, Steve Cameron, Lakshini H S Mendis, Clinton Turner, Richard L M Faull, Maurice A Curtis
In Parkinson's disease (PD), the olfactory bulb is typically the first region in the body to accumulate alpha-synuclein aggregates. This pathology is linked to decreased olfactory ability, which becomes apparent before any motor symptoms occur, and may be due to a local metal imbalance. Metal concentrations were investigated in post-mortem olfactory bulbs and tracts from 17 human subjects. Iron (p < 0.05) and sodium (p < 0.01) concentrations were elevated in the PD olfactory bulb. Combining laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry, iron and copper were evident at very low levels in regions of alpha-synuclein aggregation...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865316/oxidative-species-induced-excitonic-transport-in-tubulin-aromatic-networks-potential-implications-for-neurodegenerative-disease
#13
P Kurian, T O Obisesan, T J A Craddock
Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer's disease and Parkinson's disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. When MAP tau is degraded in tauopathic disorders, neuron dysfunction results. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood...
August 24, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28860335/activation-mechanisms-of-the-e3-ubiquitin-ligase-parkin
#14
REVIEW
Nikhil Panicker, Valina L Dawson, Ted M Dawson
Monogenetic, familial forms of Parkinson's disease (PD) only account for 5-10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin, encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated...
August 30, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28855526/therapeutic-effects-of-baicalein-on-rotenone-induced-parkinson-s-disease-through-protecting-mitochondrial-function-and-biogenesis
#15
Xue Zhang, Lida Du, Wen Zhang, Yulin Yang, Qimeng Zhou, Guanhua Du
Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD) for several decades, and disturbed mitochondrial biogenesis (mitobiogenesis) was recently found to be a common phenomenon in PD. Baicalein, a major bioactive flavone of Scutellaria baicalensis Georgi, exerted neuroprotective effects in several experimental PD models. However, the effects of baicalein in rotenone-induced PD rats and the possible mechanisms remain poorly understood. In this study, we evaluated the therapeutic effects of baicalein and explored its mechanism of action in rotenone-induced PD models...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852477/endoplasmic-reticulum-mitochondria-tethering-in-neurodegenerative-diseases
#16
REVIEW
Yi Liu, Xiongwei Zhu
Endoplasmic reticulum (ER) and mitochondria are tubular organelles with a characteristic "network structure" that facilitates the formation of inter-organellar connections. As a result, mitochondria-associated ER membranes (MAMs), a subdomain of the ER that is tightly linked to and communicates with mitochondria, serve multiple physiological functions including lipid synthesis and exchange, calcium signaling, bioenergetics, and apoptosis. Importantly, emerging evidence suggests that the abnormality and dysfunction of MAMs have been involved in various neurodegenerative disorders including Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28851515/alterations-in-the-e3-ligases-parkin-and-chip-result-in-unique-metabolic-signaling-defects-and-mitochondrial-quality-control-issues
#17
REVIEW
Britney N Lizama, Amy M Palubinsky, BethAnn McLaughlin
E3 ligases are essential scaffold proteins, facilitating the transfer of ubiquitin from E2 enzymes to lysine residues of client proteins via isopeptide bonds. The specificity of substrate binding and the expression and localization of E3 ligases can, however, endow these proteins with unique features with variable effects on mitochondrial, metabolic and CNS function. By comparing and contrasting two E3 ligases, Parkin and C-terminus of HSC70-Interacting protein (CHIP) we seek to highlight the biophysical properties that may promote mitochondrial dysfunction, acute stress signaling and critical developmental periods to cease in response to mutations in these genes...
August 26, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28851441/parkinson-s-disease-is-associated-with-dna-methylation-levels-in-human-blood-and-saliva
#18
Yu-Hsuan Chuang, Kimberly C Paul, Jeff M Bronstein, Yvette Bordelon, Steve Horvath, Beate Ritz
BACKGROUND: Several articles suggest that DNA methylation levels in blood relate to Parkinson's disease (PD) but there is a need for a large-scale study that involves suitable population based controls. The purposes of the study were: (1) to study whether PD status is associated with DNA methylation levels in blood/saliva; (2) to study whether observed associations relate to blood cell types; and (3) to characterize genome-wide significant markers ("CpGs") and clusters of CpGs (co-methylation modules) in terms of biological pathways...
August 30, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28844784/dieldrin-induced-neurotoxicity-involves-impaired-mitochondrial-bioenergetics-and-an-endoplasmic-reticulum-stress-response-in-rat-dopaminergic-cells
#19
Jordan T Schmidt, Anna Rushin, Jonna Boyda, Christopher Laurence Souders, Christopher J Martyniuk
Mitochondria are sensitive targets of environmental chemicals. Dieldrin (DLD) is an organochlorine pesticide that remains a human health concern due to high lipid bioaccumulation, and it has been epidemiologically associated to an increased risk for Parkinson's disease (PD). As mitochondrial dysfunction is involved in the etiology of PD, this study aimed to determine whether DLD impaired mitochondrial bioenergetics in dopaminergic cells. Rat immortalized dopaminergic N27 cells were treated for 24 or 48h with one dose of either a solvent control, 2...
August 24, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28843595/ginsenosides-rd-and-re-co-treatments-improve-rotenone-induced-oxidative-stress-and-mitochondrial-impairment-in-sh-sy5y-neuroblastoma-cells
#20
E González-Burgos, Carlos Fernández-Moriano, R Lozano, I Iglesias, M P Gómez-Serranillos
Oxidative stress and mitochondrial dysfunction play key roles in Parkinson's disease (PD) initiation and progression. Ginsenosides are major compounds of Ginseng species and they are responsible for pharmacological activity. The aim of this study was to investigate the potential neuroprotective effects and mechanism of the major ginsenosides Rd and Re in rotenone-induced oxidative stress model in human neuroblastoma SH-SY5Y cells. Co-treatments with both ginsenosides inhibited the increased intracellular ROS production and by-products lipid peroxidation accumulation caused by rotenone...
August 23, 2017: Food and Chemical Toxicology
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