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Parkinson's- dj-1

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https://www.readbyqxmd.com/read/29147911/dj-1-as-a-therapeutic-target-against-cancer
#1
Ji Cao, Xiaobing Chen, Meidan Ying, Qiaojun He, Bo Yang
DJ-1 is a gene involved in various cellular processes, including transcriptional regulation, oxidative stress response, fertilization, mitochondrial regulation, inflammatory and fibrogenic niche formation, and glycation damage prevention. Although a disease-associated genetic study within the past decade has demonstrated that the mutation of DJ-1 is associated with autosomal early-onset Parkinson's disease, increasing evidence suggests that DJ-1 also plays a critical role in tumor development and progression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147910/therapeutic-activities-of-dj-1-and-its-binding-compounds-against-neurodegenerative-diseases
#2
Masatoshi Inden, Daijiro Yanagisawa, Masanori Hijioka, Hiroyoshi Ariga, Yoshihisa Kitamura
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Loss-of-function mutations in the gene encoding PARK7/DJ-1 were identified in familial PD. Wild-type DJ-1 acts as an oxidative stress sensor in neural cells. Previously, we identified binding compounds of DJ-1, including UCP0045037/compound A, UCP0054278/compound B, and compound-23 (comp-23), by in silico virtual screening. These compounds prevented oxidative stress-induced dopaminergic neuronal death and restored locomotion defects in animal models of PD...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147908/dj-1-as-a-biomarker-of-parkinson-s-disease
#3
Yoshiro Saito
Parkinson's disease is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1 has been identified as a causative gene of a familial form of Parkinson's disease, PARK7, and plays a significant role in antioxidative defense, protecting cells from oxidative stress. A cysteine residue of DJ-1 at position 106 (Cys-106) is preferentially oxidized under oxidative stress. This reactive Cys-106 plays a critical role in the biological function of DJ-1, which could act as a sensor of oxidative stress by regulating antioxidative defense depending on Cys-106 oxidation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#4
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147905/transcriptional-regulation-of-dj-1
#5
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147904/the-multifaceted-roles-of-dj-1-as-an-antioxidant
#6
Prahlad V Raninga, Giovanna Di Trapani, Kathryn F Tonissen
The DJ-1 protein was originally linked with Parkinson's disease and is now known to have antioxidant functions. The protein has three redox-sensitive cysteine residues, which are involved in its dimerisation and functional properties. A mildly oxidised form of DJ-1 is the most active form and protects cells from oxidative stress conditions. DJ-1 functions as an antioxidant through a variety of mechanisms, including a weak direct antioxidant activity by scavenging reactive oxygen species. DJ-1 also regulates a number of signalling pathways, including the inhibition of apoptosis signal-regulating kinase 1 (ASK1)-induced apoptosis under oxidative stress conditions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147901/expression-of-dj-1-in-neurodegenerative-disorders
#7
Daria Antipova, Rina Bandopadhyay
In 2003, autosomal recessive loss-of-function mutations were identified in PARK7 gene that caused early-onset Parkinson's disease (PD). The PARK7 gene encodes a conserved protein termed DJ-1. DJ-1 is a ubiquitous protein, and within the brain, it is present in the nucleus and cytoplasm of both neuronal and glial cells. DJ-1 is a multifunctional protein, and numerous studies have ascribed various roles, including antioxidative properties, chaperone function, protease activities, mitochondrial functions and regulation of transcription to the protein...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147900/structural-biology-of-the-dj-1-superfamily
#8
Nathan Smith, Mark A Wilson
The DJ-1 (also called the DJ-1/PfpI, ThiJ/PfpI, or DJ-1/ThiJ/PfpI) superfamily is a structural and functional diverse group of proteins that are present in most organisms. Many of these proteins remain poorly characterized at the biochemical level, but include some known chaperones, proteases, and various stress response proteins that remain mechanistically mysterious. This chapter outlines what is known from a structural perspective about the cellular and biochemical functions of many of these proteins from distinct clades of the superfamily in several organisms...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147899/introduction-overview
#9
Hiroyoshi Ariga, Sanae M M Iguchi-Ariga
The DJ-1 gene is an oncogene and also causative gene for a familial form of Parkinson disease. Although exits of cancer and neurodegenerative diseases, including Parkinson disease, are completely opposite, there are some common points of view between both diseases, including growth and death signaling pathways, and oxidative stresses affect the onset and pathogenesis of both cancer and neurodegenerative diseases. DJ-1 has versatile functions and plays a role in protection against oxidative stress. Inactivation and/or excess activation of DJ-1 functions, therefore, leads to onsets of oxidative stress-related diseases such as type 2 diabetes and male infertility in addition to cancer and neurodegenerative diseases, and studies about DJ-1 will give rise to the common mechanism among these diseases...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29142100/abnormal-visual-gain-control-and-excitotoxicity-in-early-onset-parkinson-s-disease-drosophila-models
#10
Marc Mason Himmelberg, Ryan J H West, Christopher J H Elliott, Alex R Wade
The excitotoxic theory of Parkinson's disease (PD) hypothesises that a pathophysiological degeneration of dopaminergic neurons stems from neural hyperactivity at early stages of disease, leading to mitochondrial stress and cell death. Recent research has harnessed the visual system of Drosophila PD models to probe this hypothesis. Here, we investigate whether abnormal visual sensitivity and excitotoxicity occur in early-onset PD Drosophila models DJ-1Δ72, DJ1-Δ93, and PINK15. We used an electroretinogram to record steady state visually evoked potentials driven by temporal contrast stimuli...
November 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29124790/neuropathology-of-genetic-synucleinopathies-with-parkinsonism-review-of-the-literature
#11
REVIEW
Susanne A Schneider, Roy N Alcalay
Clinical-pathological studies remain the gold-standard for the diagnosis of Parkinson's disease (PD). However, mounting data from genetic PD autopsies challenge the diagnosis of PD based on Lewy body pathology. Most of the confirmed genetic risks for PD show heterogenous neuropathology, even within kindreds, which may or may not include Lewy body pathology. We review the literature of genetic PD autopsies from cases with molecularly confirmed PD or parkinsonism and summarize main findings on SNCA (n = 25), Parkin (n = 20, 17 bi-allelic and 3 heterozygotes), PINK1 (n = 5, 1 bi-allelic and 4 heterozygotes), DJ-1 (n = 1), LRRK2 (n = 55), GBA (n = 10 Gaucher disease patients with parkinsonism), DNAJC13, GCH1, ATP13A2, PLA2G6 (n = 8 patients, 2 with PD), MPAN (n = 2), FBXO7, RAB39B, and ATXN2 (SCA2), as well as on 22q deletion syndrome (n = 3)...
November 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29105838/a-parkinson-s-disease-gene-dj-1-repairs-brain-injury-through-sox9-stabilization-and-astrogliosis
#12
Dong-Joo Choi, Jin-Hwa Eun, Byung Gon Kim, Ilo Jou, Sang Myun Park, Eun-Hye Joe
Defects in repair of damaged brain accumulate injury and contribute to slow-developing neurodegeneration. Here, we report that a deficiency of DJ-1, a Parkinson's disease (PD) gene, delays repair of brain injury due to destabilization of Sox9, a positive regulator of astrogliosis. Stereotaxic injection of ATP into the brain striatum produces similar size of acute injury in wild-type and DJ-1-knockout (KO) mice. However, recovery of the injury is delayed in KO mice, which is confirmed by 9.4T magnetic resonance imaging and tyrosine hydroxylase immunostaining...
November 6, 2017: Glia
https://www.readbyqxmd.com/read/29097687/genome-scale-single-cell-mechanical-phenotyping-reveals-disease-related-genes-involved-in-mitotic-rounding
#13
Yusuke Toyoda, Cedric J Cattin, Martin P Stewart, Ina Poser, Mirko Theis, Teymuras V Kurzchalia, Frank Buchholz, Anthony A Hyman, Daniel J Müller
To divide, most animal cells drastically change shape and round up against extracellular confinement. Mitotic cells facilitate this process by generating intracellular pressure, which the contractile actomyosin cortex directs into shape. Here, we introduce a genome-scale microcantilever- and RNAi-based approach to phenotype the contribution of > 1000 genes to the rounding of single mitotic cells against confinement. Our screen analyzes the rounding force, pressure and volume of mitotic cells and localizes selected proteins...
November 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/29079356/parkin-overexpression-in-human-mesenchymal-stromal-cells-from-wharton-s-jelly-suppresses-6-hydroxydopamine-induced-apoptosis-potential-therapeutic-strategy-in-parkinson-s-disease
#14
A R Bonilla-Porras, A Arevalo-Arbelaez, J F Alzate-Restrepo, C Velez-Pardo, M Jimenez-Del-Rio
BACKGROUND AIMS: Stem cell transplantation is an excellent option for regenerative or replacement therapy. However, deleterious microenvironmental and endogenous factors (e.g., oxidative stress) compromise ongoing graft survival and longevity. Therefore, (transient or stable) genetically modified cells may be reasonably thought to resist oxidative stress-induced damage. Genetic engineering of mesenchymal stromal cells (MSCs) obtained from Wharton's jelly tissue may offer some therapeutic potential...
October 24, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29030185/inhibitory-effect-of-tartrate-against-phosphate-induced-dj-1-aggregation
#15
Min Soo Kim, Sangmin Lee, Sanguk Yun, Pann-Ghill Suh, Jongmi Park, Minghua Cui, Sun Choi, Sun-Shin Cha, Wook Jin
The DJ-1 protein engages in diverse cellular and pathological processes, including tumorigenesis, apoptosis, sperm fertilization, and the progression of Parkinson's disease (PD). The functional dimeric form of DJ-1 transforms into non-functional filamentous aggregates in an inorganic phosphate (Pi)-dependent manner in vitro. Here, we demonstrated that Pi and reactive oxygen species (ROS) induce DJ-1 aggregation in Neuro2A and SH-SY5Y cells. Remarkably, tartrate treatment significantly reduced Pi- and ROS-induced DJ-1 aggregation and restored Pi- and ROS-provoked cell death using quantitative data as mean±standard deviation, and statistics...
October 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29023182/potential-clinical-utility-of-multiple-system-atrophy-biomarkers
#16
Kurt A Jellinger
Multiple system atrophy (MSA), an adult-onset, fatal disorder of uncertain etiology, characterized by parkinsonism, cerebellar, autonomic and motor dysfunctions, is an α-synucleinopathy with glioneuronal degeneration involving multiple parts of the nervous system. The clinical variants correlate with the morphological phenotypes of striatonigral degeneration (MSA-P), olivoponto-cerebellar atrophy (MSA-C), and mixed type MSA. Neuropathological hallmark is the deposition of aberrant α-synuclein in glia and neurons forming cytoplasmic inclusions that cause cell dysfunction/demise...
October 23, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29021755/dj-1-inhibits-%C3%AE-synuclein-aggregation-by-regulating-chaperone-mediated-autophagy
#17
Chuan-Ying Xu, Wen-Yan Kang, Yi-Meng Chen, Tian-Fang Jiang, Jia Zhang, Li-Na Zhang, Jian-Qing Ding, Jun Liu, Sheng-Di Chen
α-Synuclein misfolding and aggregation play an important role in the pathogenesis of Parkinson's disease (PD). Loss of function and mutation of the PARK7/DJ-1 gene cause early-onset familial PD. DJ-1 can inhibit α-synuclein aggregation, and may function at an early step in the aggregation process. Soluble wild-type (WT) α-synuclein is mainly degraded by chaperone-mediated autophagy (CMA), and impairment of CMA is closely related to the pathogenesis of PD. Here, we investigated whether DJ-1 could reduce α-synuclein accumulation and aggregation by CMA...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29016861/dj-1-is-a-redox-sensitive-adapter-protein-for-high-molecular-weight-complexes-involved-in-regulation-of-catecholamine-homeostasis
#18
Dominik Piston, Lydia Alvarez-Erviti, Vikas Bansal, Daniela Gargano, Zhi Yao, Gyorgy Szabadkai, Mark Odell, M Rhyan Puno, Benny Björkblom, Jodi Maple-Grødem, Peter Breuer, Oliver Kaut, Jan Petter Larsen, Stefan Bonn, Simon Geir Møller, Ullrich Wüllner, Anthony H V Schapira, Matthew E Gegg
DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson's disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28993701/parkinson-s-disease-related-dj-1-functions-in-thiol-quality-control-against-aldehyde-attack-in-vitro
#19
Noriyuki Matsuda, Mayumi Kimura, Bruno Barros Queliconi, Waka Kojima, Masaki Mishima, Kenji Takagi, Fumika Koyano, Koji Yamano, Tsunehiro Mizushima, Yutaka Ito, Keiji Tanaka
DJ-1 (also known as PARK7) has been identified as a causal gene for hereditary recessive Parkinson's disease (PD). Consequently, the full elucidation of DJ-1 function will help decipher the molecular mechanisms underlying PD pathogenesis. However, because various, and sometimes inconsistent, roles for DJ-1 have been reported, the molecular function of DJ-1 remains controversial. Recently, a number of papers have suggested that DJ-1 family proteins are involved in aldehyde detoxification. We found that DJ-1 indeed converts methylglyoxal (pyruvaldehyde)-adducted glutathione (GSH) to intact GSH and lactate...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28962651/hexokinases-link-dj-1-to-the-pink1-parkin-pathway
#20
David N Hauser, Adamantios Mamais, Melissa M Conti, Christopher T Primiani, Ravindran Kumaran, Allissa A Dillman, Rebekah G Langston, Alexandra Beilina, Joseph H Garcia, Alberto Diaz-Ruiz, Michel Bernier, Fabienne C Fiesel, Xu Hou, Wolfdieter Springer, Yan Li, Rafael de Cabo, Mark R Cookson
BACKGROUND: Early onset Parkinson's disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 and parkin operate in pathways that preserve mitochondrial integrity, but the function of DJ-1 and how it relates to PINK1 and parkin is poorly understood. METHODS: A series of unbiased high-content screens were used to analyze changes at the protein, RNA, and metabolite level in rodent brains lacking DJ-1. Results were validated using targeted approaches, and cellular assays were performed to probe the mechanisms involved...
September 29, 2017: Molecular Neurodegeneration
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