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https://www.readbyqxmd.com/read/28627418/alterations-in-neuronal-control-of-body-weight-and-anxiety-behavior-by-glutathione-peroxidase-4-deficiency
#1
Sonja C Schriever, Annemarie Zimprich, Katrin Pfuhlmann, Peter Baumann, Florian Giesert, Valentina Klaus, Dhiraj G Kabra, Ulrich Hafen, Artem Romanov, Matthias H Tschöp, Wolfgang Wurst, Marcus Conrad, Sabine M Hölter, Daniela Vogt Weisenhorn, Paul T Pfluger
Elevated levels of oxidative stress and neuronal inflammation in the hypothalamus or ventral midbrain, respectively, represent common denominators for obesity and Parkinson's Disease (PD). However, little is known about defense mechanisms that protect neurons in these regions from oxidative damage. Here, we aimed to assess whether murine Gpx4, a crucial antioxidant enzyme that protects neurons from membrane damage and ferroptosis, is critical for the protection from neuronal inflammation in two distinct pathophysiologic diseases, namely metabolic dysfunction in diet-induced obesity or PD...
June 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28604235/discovery-validation-and-optimization-of-cerebrospinal-fluid-biomarkers-for-use-in-parkinson-s-disease
#2
Lucia Farotti, Silvia Paciotti, Anna Tasegian, Paolo Eusebi, Lucilla Parnetti
Parkinson's disease (PD) is a complex and phenotypically heterogeneous neurodegenerative disease, for which the diagnosis is mainly based on clinical parameters (even if neuroimaging plays a role in diagnostic assessment); as a consequence, misdiagnosis is common, especially in early stages. Thus, there is an urgent need of having available biomarkers in order to achieve an early and accurate diagnosis. Since molecular changes in the brain are reliably and timely reflected in cerebrospinal fluid (CSF), CSF represents an ideal source for biomarkers of different pathophysiological processes characterizing the disease since its early phases...
June 19, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28601951/acupuncture-stimulation-at-gb34-suppresses-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-oxidative-stress-in-the-striatum-of-mice
#3
Yukyung Lee, Gaeun Choi, Hyongjun Jeon, Dongsoo Kim, Sun Ryu, Sungtae Koo, Ki-Tae Ha, Seungtae Kim
Recent studies have suggested that increased oxidative stress is a potential etiology in Parkinson's disease (PD). In this study, we investigated whether acupuncture regulates antioxidants in the striatum (ST) of a PD mouse model. Male C57BL/6 mice were administered 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally once a day for 5 days and given acupuncture stimulation at SI3 or GB34 (Yanglingquan) was for 12 consecutive days. Dopaminergic neuronal survival in the nigrostriatal pathway and DJ-1 expression in the ST was evaluated by immunostaining, and the activities of superoxide dismutase (SOD) and catalase (CAT) in the ST was by enzyme-linked immunosorbent assay...
June 10, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28596309/guanine-glycation-repair-by-dj-1-park7-and-its-bacterial-homologs
#4
Gilbert Richarme, Cailing Liu, Mouadh Mihoub, Jad Abdallah, Thibaut Leger, Nicolas Joly, Jean-Claude Liebart, Ula V Jurkunas, Marc Nadal, Philippe Bouloc, Julien Dairou, Aazdine Lamouri
DNA damage induced by reactive carbonyls (mainly methylglyoxal and glyoxal), called DNA glycation, is quantitatively as important as oxidative damage. DNA glycation is associated with increased mutation frequency, DNA strand breaks, and cytotoxicity. However, in contrast to guanine oxidation repair, how glycated DNA is repaired remains undetermined. Here, we found that the parkinsonism-associated protein DJ-1 and its bacterial homologs Hsp31, YhbO and YajL could repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids...
June 8, 2017: Science
https://www.readbyqxmd.com/read/28552716/nrf2-activation-by-tauroursodeoxycholic-acid-in-experimental-models-of-parkinson-s-disease
#5
Sara Moreira, Inês Fonseca, Maria João Nunes, Alexandra Rosa, Luísa Lemos, Elsa Rodrigues, Andreia Neves Carvalho, Tiago F Outeiro, Cecília Maria Pereira Rodrigues, Maria João Gama, Margarida Castro-Caldas
Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the cause of PD remains elusive, mitochondrial dysfunction and severe oxidative stress are strongly implicated in the cell death that characterizes the disease. Under oxidative stress, the master regulator of cellular redox status, nuclear factor erythroid 2 related factor 2 (Nrf2), is responsible for activating the transcription of several cytoprotective enzymes, namely glutathione peroxidase (GPx) and heme oxygenase-1 (HO-1)...
May 25, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28541025/structural-genomic-variations-and-parkinson-s-disease
#6
Sara Bandrés-Ciga, Clara Ruz, Francisco J Barrero, Francisco Escamilla-Sevilla, Javier Pelegrina, Francisco Vives, Raquel Duran
Parkinson's disease (PD) is the second most common neurodegenerative disease, whose prevalence is projected to be between 8.7 and 9.3 million by 2030. Until about 20 years ago, PD was considered to be the textbook example of a "nongenetic" disorder. Nowadays, PD is generally considered a multifactorial disorder that arises from the combination and complex interaction of genes and environmental factors. To date, a total of 7 genes including SNCA, LRRK2, PARK2, DJ-1, PINK 1, VPS35 and ATP13A2 have been seen to cause unequivocally Mendelian PD...
May 25, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28502045/a-clinical-and-molecular-genetic-study-of-50-families-with-autosomal-recessive-parkinsonism-revealed-known-and-novel-gene-mutations
#7
Shaghayegh Taghavi, Rita Chaouni, Abbas Tafakhori, Luis J Azcona, Saghar Ghasemi Firouzabadi, Mir Davood Omrani, Javad Jamshidi, Babak Emamalizadeh, Gholam Ali Shahidi, Mona Ahmadi, Seyed Amir Hassan Habibi, Azadeh Ahmadifard, Atena Fazeli, Marzieh Motallebi, Peyman Petramfar, Saeed Askarpour, Shiva Askarpour, Hossein Ali Shahmohammadibeni, Neda Shahmohammadibeni, Hajar Eftekhari, Amir Ehtesham Shafiei Zarneh, Saeed Mohammadihosseinabad, Mehdi Khorrami, Safa Najmi, Ahmad Chitsaz, Parasto Shokraeian, Hossein Ehsanbakhsh, Jalal Rezaeidian, Reza Ebrahimi Rad, Faranak Madadi, Monavvar Andarva, Elham Alehabib, Minoo Atakhorrami, Seyed Erfan Mortazavi, Zahra Azimzadeh, Mahdis Bayat, Amir Mohammad Besharati, Mohammad Ali Harati-Ghavi, Samareh Omidvari, Zahra Dehghani-Tafti, Faraz Mohammadi, Banafsheh Mohammad Hossein Pour, Hamid Noorollahi Moghaddam, Ehsan Esmaili Shandiz, Arman Habibi, Zahra Taherian-Esfahani, Hossein Darvish, Coro Paisán-Ruiz
In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria...
May 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28458339/dj-1-park7-a-new-therapeutic-target-for-neurodegenerative-disorders
#8
Masanori Hijioka, Masatoshi Inden, Daijiro Yanagisawa, Yoshihisa Kitamura
DJ-1, encoded in a causative gene of familial Parkinson's disease (PARK7), has multiple functions: it works as an antioxidant, in transcriptional regulation, as a molecular chaperone and in protein degradation. Three types of pathogenic mutants of DJ-1 (M26I, D149A and L166P) have been reported to disrupt proper structures and lead to a loss of function. DJ-1 receives oxidation at the cysteine residue, and the degree of oxidation at the C106 residue determines DJ-1 activity. In this decade, DJ-1 has been reported to suppress the progression of various neurodegenerative disorders in animal models...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28455141/identification-of-potential-therapeutic-compounds-for-parkinson-s-disease-using-drosophila-and-human-cell-models
#9
Francisco José Sanz, Cristina Solana-Manrique, Verónica Muñoz-Soriano, Pablo Calap-Quintana, María Dolores Moltó, Nuria Paricio
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is caused by a loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrease in dopamine levels in the striatum and thus producing movement impairment. Major physiological causes of neurodegeneration in PD are oxidative stress (OS) and mitochondrial dysfunction; these pathophysiological changes can be caused by both genetic and environmental factors. Although most PD cases are sporadic, it has been shown that 5-10% of them are familial forms caused by mutations in certain genes...
April 25, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28446034/free-radicals-impair-the-anti-oxidative-stress-activity-of-dj-1-through-the-formation-of-sds-resistant-dimer
#10
Tatsuki Yasuda, Takeshi Niki, Hiroyoshi Ariga, Sanae M M Iguchi-Ariga
DJ-1 is a causative gene for familial Parkinson's disease (PD). Loss-of-function of DJ-1 protein is suggested to contribute to the onset of PD, but the causes of DJ-1 dysfunction remain insufficiently elucidated. In this study, we found that the SDS-resistant irreversible dimer of DJ-1 protein was formed in human dopaminergic neuroblastoma SH-SY5Y cells, when the cells were exposed to massive superoxide inducers such as paraquat and diquat. The dimer was also formed in vitro by superoxide in PQ redox cycling system and hydroxyl radical produced in Fenton reaction...
April 26, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28445716/trumping-neurodegeneration-targeting-common-pathways-regulated-by-autosomal-recessive-parkinson-s-disease-genes
#11
REVIEW
Laura Scott, Valina L Dawson, Ted M Dawson
Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Most PD cases are sporadic; however, rare familial forms have been identified. Autosomal recessive PD (ARPD) results from mutations in Parkin, PINK1, DJ-1, and ATP13A2, while rare, atypical juvenile ARPD result from mutations in FBXO7, DNAJC6, SYNJ1, and PLA2G6. Studying these genes and their function has revealed mitochondrial quality control, protein degradation processes, and oxidative stress responses as common pathways underlying PD pathogenesis...
April 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28385921/the-effects-of-physical-exercise-on-non-motor-symptoms-and-on-neuroimmune-rage-network-in-experimental-parkinsonism
#12
Sofia D Viana, Inês R Pita, Cristina Lemos, Daniel Rial, Patrícia Couceiro, Paulo Rodrigues-Santos, Francisco Caramelo, Félix Carvalho, Syed F Ali, Rui D Prediger, Carlos A Fontes Ribeiro, Frederico C Pereira
Parkinson's disease (PD) prodromic stages comprise neuropsychiatric perturbations that critically compromise patient's quality of life. These non-motor symptoms (NMS) are associated with exacerbated innate immunity, a hallmark of overt PD. Physical exercise (PE) has the potential to improve neuropsychiatric deficits and to modulate immune network including receptors for advanced glycation endproducts (RAGE) and Toll-like receptors (TLRs) in distinct pathological settings. Accordingly, the present study aimed to test the hypothesis that PE i) alleviates PD NMS and ii) modulates neuroimmune RAGE-network in experimental PD...
April 6, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28369333/sirt3-protects-dopaminergic-neurons-from-mitochondrial-oxidative-stress
#13
Han Shi, Han-Xiang Deng, David Gius, Paul T Schumacker, D James Surmeier, Yong-Chao Ma
Age-dependent elevation in mitochondrial oxidative stress is widely posited to be a major factor underlying the loss of substantia nigra pars compacta (SNc) dopaminergic neurons in Parkinson's disease (PD). However, mechanistic links between aging and oxidative stress are not well understood. Sirtuin-3 (Sirt3) is a mitochondrial deacetylase that could mediate this connection. Indeed, genetic deletion of Sirt3 increased oxidative stress and decreased the membrane potential of mitochondria in SNc dopaminergic neurons...
May 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28360124/genetic-mutations-linked-to-parkinson-s-disease-differentially-control-nucleolar-activity-in-pre-symptomatic-mouse-models
#14
Valentin Evsyukov, Andrii Domanskyi, Holger Bierhoff, Suzana Gispert, Rasem Mustafa, Falk Schlaudraff, Birgit Liss, Rosanna Parlato
Genetic mutations underlying neurodegenerative disorders impair ribosomal DNA (rDNA) transcription suggesting that nucleolar dysfunction could be a novel pathomechanism in polyglutamine diseases and in certain forms of amyotrophic lateral sclerosis/frontotemporal dementia. Here, we investigated nucleolar activity in pre-symptomatic digenic models of Parkinson's disease (PD) that model the multifactorial aetiology of this disease. To this end, we analysed a novel mouse model mildly overexpressing mutant human α-synuclein (hA53T-SNCA) in a PTEN-induced kinase 1 (PINK1/PARK6) knockout background and mutant mice lacking both DJ-1 (also known as PARK7) and PINK1...
May 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28348719/bag5-interacts-with-dj-1-and-inhibits-the-neuroprotective-effects-of-dj-1-to-combat-mitochondrial-oxidative-damage
#15
Li-Xia Qin, Jie-Qiong Tan, Hai-Nan Zhang, Kousar Rizwana, Jia-Hong Lu, Jian-Guang Tang, Bo Jiang, Xiang-Min Shen, Ji-Feng Guo, Bei-Sha Tang, Li-Ming Tan, Chun-Yu Wang
Loss-of-function mutations in gene encoding DJ-1 contribute to the pathogenesis of autosomal recessive early-onset familial forms of Parkinson's disease (PD). DJ-1 is a multifunctional protein and plays a protective role against oxidative stress-induced mitochondrial damage and cell death, but the exact mechanism underlying this is not yet clearly understood. Here, using coimmunoprecipitation (Co-IP) and immunofluorescence methods, we prove that Bcl-2-associated athanogene 5 (BAG5), a BAG family member, interacts with DJ-1 in mammalian cells...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28330770/dj-1-a-parkinson-s-disease-related-protein-aggregates-under-denaturing-conditions-and-co-aggregates-with-%C3%AE-synuclein-through-hydrophobic-interaction
#16
Min Zhu, Shivaliben H Patel, Shubo Han
BACKGROUND: DJ-1, a small ubiquitously expressed protein implicated in several pathways associated with Parkinson's disease pathogenesis, has been found to interact with α-synuclein and modulate its aggregation, yet the exact mechanisms remain unclear. METHODS: The stability and aggregation properties of wild-type DJ-1 under denaturing conditions, such as low pH, high temperature, presence of denaturants were investigated. The interaction between DJ-1 and α-synuclein was tested by SDS-PAGE gel and native gel electrophoresis and by size-exclusion HPLC...
March 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28289797/-epidemiology-and-causes-of-parkinson-s-disease
#17
C M Lill, C Klein
Parkinson's disease (PD) is the second most common neurodegenerative disease and has a growing socioeconomic impact due to demographic changes in the industrial nations. There are several forms of PD, a fraction of which (<5%) are monogenic, i. e. caused by mutations in single genes. At present, six genes have been established for the clinically classical form of parkinsonism including three autosomal dominantly (SNCA, LRRK2, VPS35) and three autosomal recessively inherited ones (Parkin, PINK1, DJ-1)...
April 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28273718/mechanisms-of-parkinson-s-disease-related-proteins-in-mediating-secondary-brain-damage-after-cerebral-ischemia
#18
TaeHee Kim, Raghu Vemuganti
Both Parkinson's disease (PD) and stroke are debilitating conditions that result in neuronal death and loss of neurological functions. These two conditions predominantly affect aging populations with the deterioration of the quality of life for the patients themselves and a tremendous burden to families. While the neurodegeneration and symptomology of PD develop chronically over the years, post-stroke neuronal death and dysfunction develop rapidly in days. Despite the discrepancy in the pathophysiological time frame and severity, both conditions share common molecular mechanisms that include oxidative stress, mitochondrial dysfunction, inflammation, endoplasmic reticulum stress, and activation of various cell death pathways (apoptosis/necrosis/autophagy) that synergistically modulate the neuronal death...
June 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28258548/backbone-resonance-assignments-of-the-escherichia-coli-62%C3%A2-kda-protein-hsp31
#19
Jihong Kim, Dongwook Choi, Chankyu Park, Kyoung-Seok Ryu
Dimeric Hsp31 protein was first characterized as a holding chaperone of Escherichia coli (E. coli), and has been suggested as having protease activity due to the presence of a potential catalytic triad, Cys185, His186, and Asp214. However, it has recently been reported that Hsp31 displays a relatively strong glyoxalase III activity that can decompose reactive carbonyl species (methylglyoxal and glyoxal) in the absence of additional cofactor. Hsp31 is a representative member of the DJ-1/ThiJ/PfpI protein superfamily, and the importance of DJ-1 protein in Parkinson's disease has been well known...
March 3, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28246362/toxoplasma-dj-1-regulates-organelle-secretion-by-a-direct-interaction-with-calcium-dependent-protein-kinase-1
#20
Matthew A Child, Megan Garland, Ian Foe, Peter Madzelan, Moritz Treeck, Wouter A van der Linden, Kristina Oresic Bender, Eranthie Weerapana, Mark A Wilson, John C Boothroyd, Michael L Reese, Matthew Bogyo
Human DJ-1 is a highly conserved and yet functionally enigmatic protein associated with a heritable form of Parkinson's disease. It has been suggested to be a redox-dependent regulatory scaffold, binding to proteins to modulate their function. Here we present the X-ray crystal structure of the Toxoplasma orthologue Toxoplasma gondii DJ-1 (TgDJ-1) at 2.1-Å resolution and show that it directly associates with calcium-dependent protein kinase 1 (CDPK1). The TgDJ-1 structure identifies an orthologously conserved arginine dyad that acts as a phospho-gatekeeper motif to control complex formation...
February 28, 2017: MBio
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