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Parkinson's- dj-1

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https://www.readbyqxmd.com/read/29315581/parkinson-disease-related-dj-1-modulates-the-expression-of-uncoupling-protein-4-against-oxidative-stress
#1
Shaoqing Xu, Xiaodong Yang, Yiwei Qian, Qin Xiao
Loss of function mutations of DJ-1 (PARK7) have been linked to the pathogenesis of Parkinson disease (PD). Antioxidative stress is one of the multi-protective functions of DJ-1, and oxidation of cysteine 106 (Cys106) has been proposed to regulate the protective activity of DJ-1. Uncoupling protein 4 (UCP4) is located in the inner membrane of mitochondria and functions to protect against oxidative stress. In this study, we used neuronal (SH-SY5Y) cells and DJ-1 knockout (KO) mice to elucidate whether DJ-1 regulated oxidative stress via modulating the expression of UCP4, and the underlying mechanism...
January 8, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29285276/pilot-study-molecular-risk-factors-for-diagnosing-sporadic-parkinson-s-disease-based-on-gene-expression-in-blood-in-mptp-induced-rhesus-monkeys
#2
Liangqin Shi, Chao Huang, Qihui Luo, Yu Xia, Heng Liu, Like Li, Wentao Liu, Wenjing Ma, Jing Fang, Li Tang, Wen Zeng, Zhengli Chen
Clinical diagnosis of Parkinson's disease (PD) is characterized by the classical features of tremor, bradykinesia and rigidity, which are present only when more than 70%-80% degeneration of dopaminergic (DA) neurons in the substantia nigra. The lack of means for early diagnosis of PD has elicited interest in searching for its risk factors, which, by now, are almost obtained at a single time point in PD process, and little developing risk factors, obtained from completely normal situation to the onset or even advanced stage of PD in individual person which could monitor the progress of PD, are present...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29258409/effect-of-dj-1-downregulation-on-the-functions-of-the-first-trimester-extravillous-trophoblasts
#3
Han-Sung Kwon, Ji Hyun Park, Han-Sung Hwang, In-Sook Sohn, Young-Han Kim, SiHyun Cho
DJ-1 ( PARK7) has been reported to be causative gene of Parkinson disease and also an oncogene. A loss in DJ-1 function can lead to cell death in neurodegenerative disease, or a gain of it can cause unregulated cell survival in cancer, respectively. DJ-1 protein is known to be expressed mainly in trophoblastic cells in the placenta with increased expression in the first trimester compared to later in term. However, its role in trophoblast regulation remains unknown. This study aimed to investigate the effect of DJ-1 regulation on a first trimester extravillous trophoblast cell line, HTR-8/SVneo...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29241707/expression-of-the-dj-1-protein-in-the-serum-of-chinese-patients-with-parkinson-s-disease
#4
Chunna An, Xiaoping Pu, Weizhong Xiao, Hongning Zhang
DJ-1 is one of the important genes found in Parkinson's disease (PD). Studies have shown that the DJ-1 protein levels are elevated in the cerebrospinal fluid (CSF) and plasma of sporadic PD patients, and the DJ-1 protein levels in the CSF and plasma may serve as biomarkers of PD. However, Japanese scholars previously reported that there was no difference in the levels of the DJ-1 protein in serum between sporadic PD patients and controls. Therefore, whether the serum DJ-1 protein levels are different between PD patients and controls in Chinese patients as well as whether serum DJ-1 protein can serve as a biomarker of PD are unknown...
December 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29234413/salidroside-protects-against-mpp-induced-neuronal-injury-through-dj-1-nrf2-antioxidant-pathway
#5
Leitao Wu, Hang Xu, Liang Cao, Tao Li, Ruru Li, Yang Feng, Jianzong Chen, Jing Ma
Parkinson's disease (PD) is the second most common neurodegenerative disorder. We have found that salidroside (Sal) exhibited neuroprotective effects against MPP+ toxicity. However, the molecular mechanism is not fully understood. In this study, we found that Sal significantly prevented MPP+-induced decrease of mRNA and protein expression of Nrf2, GCLc, SOD1, and SOD2 in SH-SY5Y cells. Moreover, silencing of Nrf2 significantly inhibited Sal-induced increase in mRNA and protein expression of GCLc, SOD1, and SOD2...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29218631/intracellular-metal-binding-and-redox-behavior-of-human-dj-1
#6
Letizia Barbieri, Enrico Luchinat, Lucia Banci
DJ-1 is a conserved, ubiquitous protein associated to a large number of intracellular processes. Human DJ-1 has been linked to several pathologies, including hereditary forms of Parkinson's disease, cancer, and amyotrophic lateral sclerosis. Several cytoprotective functions of DJ-1 have been reported, however, its actual mechanisms of action remain elusive. In vitro, DJ-1 has been shown to bind zinc and copper(II) at its active site, which contains a conserved cysteine (C106), and copper(I) at a different binding site...
December 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29200905/mptp-induced-vulnerability-of-dopamine-neurons-in-a53t-%C3%AE-synuclein-overexpressed-mice-with-the-potential-involvement-of-dj-1-downregulation
#7
Seongmi Lee, Seung Tack Oh, Ha Jin Jeong, Sok Cheon Pak, Hi-Joon Park, Jongpil Kim, Hyun-Seok Cho, Songhee Jeon
Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the α-synuclein (α-syn) gene. Mutant α-syn expression increases the vulnerability of neurons to exogenous insults. In this study, we developed a new PD model in the transgenic mice expressing mutant hemizygous (hemi) or homozygous (homo) A53T α-synuclein (α-syn Tg) and their wildtype (WT) littermates by treatment with sub-toxic (10 mg/kg, i.p., daily for 5 days) or toxic (30 mg/kg, i.p., daily for 5 days) dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
November 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29183158/critical-roles-of-glutaredoxin-in-brain-cells-implications-for-parkinson-s-disease
#8
Olga Gorelenkova Miller, John J Mieyal
SIGNIFICANCE: Glutaredoxin (Grx1), an evolutionarily conserved and ubiquitous enzyme, regulates redox signal transduction and protein redox homeostasis by catalyzing reversible S-glutathionylation. Grx1 plays different roles in different cell types. In Parkinson's disease (PD), Grx1 regulates apoptosis signaling in dopaminergic neurons, so that loss of Grx1 leads to increased cell death; in microglial cells, Grx1 regulates pro-inflammatory signaling, so that upregulation of Grx1 promotes cytokine production...
November 28, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29180793/activation-of-the-mitochondrial-unfolded-protein-response-promotes-longevity-and-dopamine-neuron-survival-in-parkinson-s-disease-models
#9
Jason F Cooper, Emily Machiela, Dylan J Dues, Katie K Spielbauer, Megan M Senchuk, Jeremy M Van Raamsdonk
While the pathogenesis of Parkinson's disease (PD) is incompletely understood, mitochondrial dysfunction is thought to play a crucial role in disease pathogenesis. Here, we examined the relationship between mitochondrial function and dopamine neuron dysfunction and death using C. elegans mutants for three mitochondria-related genes implicated in monogenic PD (pdr-1/PRKN, pink-1/PINK1 and djr-1.1/DJ-1). We found that pdr-1 and pink-1 mutants exhibit deficits in dopamine-dependent behaviors, but no loss of dopamine neurons, while djr-1...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29177768/familial-parkinson-s-disease-associated-l166p-mutant-dj-1-is-cleaved-by-mitochondrial-serine-protease-omi-htra2
#10
Kai Fu, Yanfei Wang, Dongkai Guo, Guanghui Wang, Haigang Ren
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in the DJ-1, including L166P, are responsible for recessive early-onset PD. Many lines of evidence have shown that L166P is not only a loss-of-function mutant, but also a pro-apoptotic-like protein that results in mitochondrial dysfunction. L166P has been reported to be unstable and to mislocalize to mitochondria. However, the mechanisms underlying the instability of L166P compared to wild-type DJ-1 remain largely unknown...
November 24, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29175327/structural-basis-for-the-interaction-between-dj-1-and-bcl-xl
#11
Mi-Kyung Lee, Min-Sung Lee, Da-Woon Bae, Dong-Hwa Lee, Sun-Shin Cha, Seung-Wook Chi
DJ-1 is a multifunctional protein associated with Parkinson's disease (PD) and tumorigenesis. In response to ultraviolet B (UVB) irradiation, DJ-1 is translocated into the mitochondria, and its interaction with the mitochondrial protein Bcl-XL protects cells against death. In this study, we characterized the molecular interaction between DJ-1 and Bcl-XL by NMR spectroscopy. The NMR chemical shift perturbation data demonstrated that the oxidized but not the reduced form of DJ-1 binds to the predominantly hydrophobic groove surrounded by the BH1-BH3 domains in Bcl-XL...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29147911/dj-1-as-a-therapeutic-target-against-cancer
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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