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Parkinson's- dj-1

Chien-Wei Feng, Han-Chun Hung, Shi-Ying Huang, Chun-Hong Chen, Yun-Ru Chen, Chun-Yu Chen, San-Nan Yang, Hui-Min David Wang, Ping-Jyun Sung, Jyh-Horng Sheu, Kuan-Hao Tsui, Wu-Fu Chen, Zhi-Hong Wen
Parkinson's disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways...
October 17, 2016: Marine Drugs
Kelly L Stauch, Lance M Villeneuve, Phillip R Purnell, Sanjit Pandey, Chittibabu Guda, Howard S Fox
This article reports changes in the striatal non-synaptic mitochondrial proteome of DJ-1, Parkin, and PINK1 knockout (KO) rats at 3 months of age. DJ-1, Parkin, and PINK1 mutations cause autosomal-recessive parkinsonism. It is thought that loss of function of these proteins contributes to the onset and pathogenesis of Parkinson׳s disease (PD). As DJ-1, Parkin, and PINK1 have functions in the regulation of mitochondria, the dataset generated here highlights protein expression changes, which can be helpful for understanding pathological mitochondrial alterations...
December 2016: Data in Brief
Qingye Li, Yuxian Tang, Jing Qin, Lan Yi, Yening Yang, Juan Wang, Jie He, Qi Su, Hui Tan
Diallyl disulfide (DADS) has been demonstrated to exert potent anticancer effects in vitro and in vivo. Previous studies indicate that DADS may induce the differentiation and/or apoptosis of human leukemia cells in vitro. However, the mechanisms underlying these anticancer effects remain elusive. The aim of the present study was to investigate alterations in the subcellular localization of protein deglycase DJ‑1 (also known as Parkinsonism associated deglycase-7, PARK-7) in the cytoplasm, nucleus and mitochondria of human leukemia HL‑60 cells induced by DADS, in order to provide novel experimental evidence for the molecular mechanisms underlying the anticancer mechanisms of DADS in leukemia cells...
October 12, 2016: Molecular Medicine Reports
Prahlad V Raninga, Giovanna Di Trapani, Slavica Vuckovic, Kathryn F Tonissen
Multiple myeloma (MM) is an incurable plasma B cell malignancy. Despite recent advancements in anti-MM therapies, development of drug resistance remains a major clinical hurdle. DJ-1, a Parkinson's disease-associated protein, is upregulated in many cancers and its knockdown suppresses tumor growth and overcomes chemoresistance. However, the role of DJ-1 in MM remains unknown. Using gene expression databases we found increased DJ-1 expression in MM patient cells, which correlated with shorter overall survival and poor prognosis in MM patients...
October 12, 2016: Apoptosis: An International Journal on Programmed Cell Death
Roman Tatura, Theo Kraus, Armin Giese, Thomas Arzberger, Malte Buchholz, Günter Höglinger, Ulrich Müller
INTRODUCTION: In order to better understand the role of epigenetic influences in the etiology of Parkinson's disease (PD), we studied the expression of microRNAs in gyri cinguli of patients and controls. METHODS: Expression profiling of 744 well-characterized microRNAs in gyri cinguli from patients and controls using TaqMan array microRNA cards. Verification of significantly dysregulated microRNAs by SYBR Green qRT-PCR. RESULTS: First screen by TaqMan array identified 43 microRNAs that were upregulated in gyri cinguli from patients...
September 28, 2016: Parkinsonism & related Disorders
Yoshihisa Kitamura, Masatoshi Inden, Yasuto Kimoto, Kazuyuki Takata, Daijiro Yanagisawa, Masanori Hijioka, Eishi Ashihara, Ikuo Tooyama, Shun Shimohama, Hiroyoshi Ariga
Previously, DJ-1 modulator UCP0054278/comp-B was identified by virtual screening, where comp-B interacts with DJ-1 to produce antioxidant and neuroprotective responses in Parkinson's disease models. However, the effect of comp-B in an in vivo Alzheimer's disease (AD) model is yet undetermined. Thus, we examined the effect of comp-B on spatial learning, memory, and amyloid-β (Aβ) clearance in a transgenic mouse model of AD. We found that comp-B resolved the cognitive deficits, reduced insoluble Aβ42 levels, and prevented the degeneration of synaptic functions, thereby suggesting that comp-B may become a major compound for AD treatment...
September 21, 2016: Journal of Alzheimer's Disease: JAD
Ya-Ping Yan, Bo Zhang, Yan-Fang Mao, Zhang-Yu Guo, Jun Tian, Guo-Hua Zhao, Jia-Li Pu, Wei Luo, Zhi-Yuan Ouyang, Bao-Rong Zhang
Dopa-responsive dystonia (DRD) comprises a heterogeneous group of movement disorders. A limited number of studies of Chinese patients with DRD have been reported. In the present study, we investigated the clinical and genetic features of 12 Chinese DRD families. Point mutation analysis of the GTP-cyclohydrolase I (GCH1), tyrosine hydroxylase (TH) and sepiapterin reductase (SPR) genes was conducted by direct sequencing. In addition, multiplex ligation-dependent probe amplification targeting GCH1 and TH was performed in "mutation-free" patients...
October 5, 2016: International Journal of Neuroscience
Gunnar F Kwakye, Rachael A McMinimy, Michael Aschner
Human disease commonly manifests as a result of complex genetic and environmental interactions. In the case of neurodegenerative diseases, such as Parkinson's disease (PD), understanding how environmental exposures collude with genetic polymorphisms in the central nervous system to cause dysfunction is critical in order to develop better treatment strategies, therapies, and a more cohesive paradigm for future research. The intersection of genetics and the environment in disease etiology is particularly relevant in the context of their shared pathophysiological mechanisms...
September 9, 2016: Neurochemical Research
Francesca Morgante, Alfonso Fasano, Monia Ginevrino, Simona Petrucci, Lucia Ricciardi, Francesco Bove, Chiara Criscuolo, Marcello Moccia, Anna De Rosa, Chiara Sorbera, Anna Rita Bentivoglio, Paolo Barone, Giuseppe De Michele, Maria Teresa Pellecchia, Enza Maria Valente
OBJECTIVE: The aim of this multicenter, case-control study was to investigate the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease (PD) compared to a group of patients without the mutation. METHODS: We compared 22 patients with biallelic parkin mutations (parkin-PD) and 26 patients negative for parkin, PINK1, DJ-1, and GBA mutations (PD-NM), matched for age at onset, disease duration, levodopa, and dopamine agonist equivalent daily dose...
October 4, 2016: Neurology
Shu Zhang, Seema Mukherjee, Xuejun Fan, Ahmad Salameh, Kalpana Mujoo, Zhao Huang, Leike Li, Georgina To'a Salazar, Ningyan Zhang, Zhiqiang An
HER3/ErbB3 has emerged as a new therapeutic target for cancer. Currently, more than a dozen anti-HER3 antibodies are in clinical trials for treatment of various cancers. However, limited understanding of the complex HER3 signaling in cancer and lack of established biomarkers have made it challenging to stratify cancer patients who can benefit from HER3 targeted therapies. In this study, we identified DJ-1/PARK7 (Parkinson Protein 7) as a novel interaction partner of HER3 and demonstrated the potential of DJ-1 as a biomarker for anti-HER3 cancer therapy...
August 25, 2016: Oncotarget
Nuramatjan Ablat, Deyong Lv, Rutong Ren, Yilixiati Xiaokaiti, Xiang Ma, Xin Zhao, Yi Sun, Hui Lei, Jiamin Xu, Yingcong Ma, Xianrong Qi, Min Ye, Feng Xu, Hongbin Han, Xiaoping Pu
Parkinson's disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L.) has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD...
August 24, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Emmanuel Vázquez-Mayorga, Ángel G Díaz-Sánchez, Ruben K Dagda, Carlos A Domínguez-Solís, Raul Y Dagda, Cynthia K Coronado-Ramírez, Alejandro Martínez-Martínez
Mutations the in human DJ-1 (hDJ-1) gene are associated with early-onset autosomal recessive forms of Parkinson's disease (PD). hDJ-1/parkinsonism associated deglycase (PARK7) is a cytoprotective multi-functional protein that contains a conserved cysteine-protease domain. Given that cysteine-proteases can act on both amide and ester substrates, we surmised that hDJ-1 possessed cysteine-mediated esterase activity. To test this hypothesis, hDJ-1 was overexpressed, purified and tested for activity towards 4-nitrophenyl acetate (pNPA) as µmol of pNPA hydrolyzed/min/mg·protein (U/mg protein)...
2016: International Journal of Molecular Sciences
Eunju Im, Lang Yoo, Minju Hyun, Woo Hyun Shin, Kwang Chul Chung
Parkinson's disease (PD) is characterized by selective loss of dopaminergic neurons in the pars compacta of the substantia nigra and accumulation of ubiquitinated proteins in aggregates called Lewy bodies. Several mutated genes have been found in familial PD patients, including SNCA (α-synuclein), PARK2 (parkin), PINK1, PARK7 (DJ-1), LRRK2 and ATP13A2 Many pathogenic mutations of PARK2, which encodes the ubiquitin E3 ligase parkin, result in loss of function, leading to accumulation of parkin substrates and consequently contributing to dopaminergic cell death...
August 2016: Open Biology
Haidy E Michel, Mariane G Tadros, Ahmed Esmat, Amani E Khalifa, Ahmed M Abdel-Tawab
Parkinson's disease (PD) is a slowly progressive neurodegenerative movement disorder. Apoptosis, neuroinflammation, and oxidative stress are the current hypothesized mechanisms for PD pathogenesis. Tetramethylpyrazine (TMP), the major bioactive component of Ligusticum wallichii Franchat (ChuanXiong), Family Apiaceae, reportedly has anti-apoptotic, anti-inflammatory and antioxidant effects. This study investigated the role of 'TMP' in preventing rotenone-induced neurobiological and behavioral sequelae. A preliminary dose-response study was conducted where rats received TMP (10, 20, and 40 mg/kg, i...
August 11, 2016: Molecular Neurobiology
Yuetao Zhou, Xiaolong Shi, Hong Chen, Shaqiu Zhang, Madhuri S Salker, Andreas F Mack, Michael Föller, Tak W Mak, Yogesh Singh, Florian Lang
DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na(+) /H(+) exchanger 1 (NHE1). ROS formation in CD4(+) T cells plays a decisive role in regulating inflammatory responses. In the present study we explored whether DJ-1 is expressed in CD4(+) T cells and affects ROS production as well as NHE1 in those cells...
August 10, 2016: Journal of Cellular Physiology
Yoshiro Saito, Yoko Akazawa-Ogawa, Akihiro Matsumura, Kazumasa Saigoh, Sayoko Itoh, Kenta Sutou, Mayuka Kobayashi, Yuichiro Mita, Mototada Shichiri, Shin Hisahara, Yasuo Hara, Harutoshi Fujimura, Hiroyuki Takamatsu, Yoshihisa Hagihara, Yasukazu Yoshida, Takao Hamakubo, Susumu Kusunoki, Shun Shimohama, Noriko Noguchi
Parkinson's disease (PD) is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1, the product of the causative gene of a familial form of PD, plays a significant role in anti-oxidative defence to protect cells from oxidative stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position 106 (Cys-106) under oxidative stress. Here, using specific antibodies against Cys-106-oxidized DJ-1 (oxDJ-1), it was found that the levels of oxDJ-1 in the erythrocytes of unmedicated PD patients (n = 88) were higher than in those of medicated PD patients (n = 62) and healthy control subjects (n = 33)...
2016: Scientific Reports
M Di Nottia, M Masciullo, D Verrigni, S Petrillo, A Modoni, V Rizzo, D Di Giuda, T Rizza, M Niceta, A Torraco, M Bianchi, M Santoro, A R Bentivoglio, E Bertini, F Piemonte, R Carrozzo, G Silvestri
DJ-1 mutations are associated to early-onset Parkinson's disease and accounts for about 1-2% of the genetic forms. The protein is involved in many biological processes and its role in mitochondrial regulation is gaining great interest, even if its function in mitochondria is still unclear. We describe a 47-year-old woman affected by a multisystem disorder characterized by progressive, early-onset parkinsonism plus distal spinal amyotrophy, cataracts and sensory-neural deafness associated with a novel homozygous c...
October 6, 2016: Clinical Genetics
Sevda Erer, Unal Egeli, Mehmet Zarifoglu, Gulcin Tezcan, Gulsah Cecener, Berrin Tunca, Secil Ak, Elif Demirdogen, Gulay Kenangil, Hakan Kaleagası, Okan Dogu, Esen Saka, Bulent Elibol
OBJECTIVE: Variations in PARK genes (PRKN, PINK1, DJ-1, and SNCA) cause early-onset Parkinson's disease (EOPD) in different populations. In the current study, we aimed to evaluate the frequencies of variations in PARK genes and the effects of these variations on the phenotypes of Turkish EOPD patients. METHODS: All coding regions and exon-intron boundaries of the PRKN, PINK1, DJ-1, and SNCA genes were screened by heteroduplex analysis followed by direct sequencing of the detected variants in 50 Turkish EOPD patients...
September 2016: Clinical Neurology and Neurosurgery
Jin-Mo Kim, Seon-Heui Cha, Yu Ree Choi, Ilo Jou, Eun-Hye Joe, Sang Myun Park
Parkinson's disease (PD) is a common chronic and progressive neurodegenerative disorder. Although the cause of PD is still poorly understood, mutations in many genes including SNCA, parkin, PINK1, LRRK2, and DJ-1 have been identified in the familial forms of PD. It was recently proposed that alterations in lipid rafts may cause the neurodegeneration shown in PD. Here, we observe that DJ-1 deficiency decreased the expression of flotillin-1 (flot-1) and caveolin-1 (cav-1), the main protein components of lipid rafts, in primary astrocytes and MEF cells...
2016: Scientific Reports
Waka Kojima, Yuki Kujuro, Kei Okatsu, Queliconi Bruno, Fumika Koyano, Mayumi Kimura, Koji Yamano, Keiji Tanaka, Noriyuki Matsuda
DJ-1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK7 locus. Consistent with the inferred correlation between Parkinson's disease and mitochondrial impairment, mitochondrial localization of DJ-1 and its implied role in mitochondrial quality control have been reported. However, the mechanism by which DJ-1 affects mitochondrial function remains poorly defined, and the mitochondrial localization of DJ-1 is still controversial...
July 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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