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Genetics of Parkinson\u2019s disease. <i>Cold Spring Harb. Perspect. Med.<\/i>, <b>2<\/b>, a008888 (2012).","DOI":"10.1101\/cshperspect.a008888"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson\u2019s disease. <i>Annu. Rev. Neurosci.<\/i>, <b>28<\/b>, 57\u201387 (2005).","DOI":"10.1146\/annurev.neuro.28.061604.135718"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. <i>Science<\/i>, <b>299<\/b>, 256\u2013259 (2003).","DOI":"10.1126\/science.1077209"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Bonifati V, Oostra BA, Heutink P. Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson\u2019s disease. <i>J. Mol. Med.<\/i> (Berl.), <b>82<\/b>, 163\u2013174 (2004).","DOI":"10.1007\/s00109-003-0512-1"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Tao X, Tong L. Crystal structure of human DJ-1, a protein associated with early onset Parkinson\u2019s disease. <i>J. Biol. Chem.<\/i>, <b>278<\/b>, 31372\u201331379 (2003).","DOI":"10.1074\/jbc.M304221200"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Olzmann JA, Brown K, Wilkinson KD, Rees HD, Huai Q, Ke H, Levey AI, Li L, Chin LS. Familial Parkinson\u2019s disease-associated L166P mutation disrupts DJ-1 protein folding and function. <i>J. Biol. Chem.<\/i>, <b>279<\/b>, 8506\u20138515 (2004).","DOI":"10.1074\/jbc.M311017200"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Ito G, Ariga H, Nakagawa Y, Iwatsubo T. Roles of distinct cysteine residues in <i>S<\/i>-nitrosylation and dimerization of DJ-1. <i>Biochem. Biophys. Res. Commun.<\/i>, <b>339<\/b>, 667\u2013672 (2006).","DOI":"10.1016\/j.bbrc.2005.11.058"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Choi MS, Nakamura T, Cho SJ, Han X, Holland EA, Qu J, Petsko GA, Yates JR 3rd, Liddington RC, Lipton SA. Transnitrosylation from DJ-1 to PTEN attenuates neuronal cell death in Parkinson\u2019s disease models. <i>J. Neurosci.<\/i>, <b>34<\/b>, 15123\u201315131 (2014).","DOI":"10.1523\/JNEUROSCI.4751-13.2014"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Wilson MA. The role of cysteine oxidation in DJ-1 function and dysfunction. <i>Antioxid. Redox Signal.<\/i>, <b>15<\/b>, 111\u2013122 (2011).","DOI":"10.1089\/ars.2010.3481"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Ariga H, Takahashi-Niki K, Kato I, Maita H, Niki T, Iguchi-Ariga SM. Neuroprotective function of DJ-1 in Parkinson\u2019s disease. <i>Oxid. Med. Cell. Longev.<\/i>, <b>2013<\/b>, 683920 (2013).","DOI":"10.1155\/2013\/683920"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Kinumi T, Kimata J, Taira T, Ariga H, Niki E. Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation <i>in vivo<\/i> in human umbilical vein endothelial cells. <i>Biochem. Biophys. Res. Commun.<\/i>, <b>317<\/b>, 722\u2013728 (2004).","DOI":"10.1016\/j.bbrc.2004.03.110"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H. DJ-1 has a role in antioxidative stress to prevent cell death. <i>EMBO Rep.<\/i>, <b>5<\/b>, 213\u2013218 (2004).","DOI":"10.1038\/sj.embor.7400074"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Yanagisawa D, Kitamura Y, Inden M, Takata K, Taniguchi T, Morikawa S, Morita M, Inubushi T, Tooyama I, Taira T, Iguchi-Ariga SM, Akaike A, Ariga H. DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats. <i>J. Cereb. Blood Flow Metab.<\/i>, <b>28<\/b>, 563\u2013578 (2008).","DOI":"10.1038\/sj.jcbfm.9600553"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Inden M, Taira T, Kitamura Y, Yanagida T, Tsuchiya D, Takata K, Yanagisawa D, Nishimura K, Taniguchi T, Kiso Y, Yoshimoto K, Agatsuma T, Koide-Yoshida S, Iguchi-Ariga SM, Shimohama S, Ariga H. PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson\u2019s disease rat model. <i>Neurobiol. Dis.<\/i>, <b>24<\/b>, 144\u2013158 (2006).","DOI":"10.1016\/j.nbd.2006.06.004"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Martinat C, Shendelman S, Jonason A, Leete T, Beal MF, Yang L, Floss T, Abeliovich A. Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES-derived cell model of primary Parkinsonism. <i>PLoS Biol.<\/i>, <b>2<\/b>, e327 (2004).","DOI":"10.1371\/journal.pbio.0020327"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Im JY, Lee KW, Junn E, Mouradian MM. DJ-1 protects against oxidative damage by regulating the thioredoxin\/ASK1 complex. <i>Neurosci. Res.<\/i>, <b>67<\/b>, 203\u2013208 (2010).","DOI":"10.1016\/j.neures.2010.04.002"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Im JY, Lee KW, Woo JM, Junn E, Mouradian MM. DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway. <i>Hum. Mol. Genet.<\/i>, <b>21<\/b>, 3013\u20133024 (2012).","DOI":"10.1093\/hmg\/dds131"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Xu J, Zhong N, Wang H, Elias JE, Kim CY, Woldman I, Pifl C, Gygi SP, Geula C, Yankner BA. The Parkinson\u2019s disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis. <i>Hum. Mol. Genet.<\/i>, <b>14<\/b>, 1231\u20131241 (2005).","DOI":"10.1093\/hmg\/ddi134"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Fan J, Ren H, Jia N, Fei E, Zhou T, Jiang P, Wu M, Wang G. DJ-1 decreases Bax expression through repressing p53 transcriptional activity. <i>J. Biol. Chem.<\/i>, <b>283<\/b>, 4022\u20134030 (2008).","DOI":"10.1074\/jbc.M707176200"},{"key":"20","unstructured":"20) Niki T, Takahashi-Niki K, Taira T, Iguchi-Ariga SM, Ariga H. DJBP: a novel DJ-1-binding protein negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex. <i>Mol. Cancer Res.<\/i>, <b>1<\/b>, 247\u2013261 (2003)."},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Takahashi K, Taira T, Niki T, Seino C, Iguchi-Ariga SM, Ariga H. DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor. <i>J. Biol. Chem.<\/i>, <b>276<\/b>, 37556\u201337563 (2001).","DOI":"10.1074\/jbc.M101730200"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Yamaguchi S, Yamane T, Takahashi-Niki K, Kato I, Niki T, Goldberg MS, Shen J, Ishimoto K, Doi T, Iguchi-Ariga SM, Ariga H. Transcriptional activation of low-density lipoprotein receptor gene by DJ-1, and effect of DJ-1 on cholesterol homeostasis. <i>PLoS ONE<\/i>, <b>7<\/b>, e38144 (2012).","DOI":"10.1371\/journal.pone.0038144"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Ishikawa S, Taira T, Takahashi-Niki K, Niki T, Ariga H, Iguchi-Ariga SM. Human DJ-1-specific transcriptional activation of tyrosine hydroxylase gene. <i>J. Biol. Chem.<\/i>, <b>285<\/b>, 39718\u201339731 (2010).","DOI":"10.1074\/jbc.M110.137034"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Shendelman S, Jonason A, Martinat C, Leete T, Abeliovich A. DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation. <i>PLoS Biol.<\/i>, <b>2<\/b>, e362 (2004).","DOI":"10.1371\/journal.pbio.0020362"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Sajjad MU, Green EW, Miller-Fleming L, Hands S, Herrera F, Campesan S, Khoshnan A, Outeiro TF, Giorgini F, Wyttenbach A. DJ-1 modulates aggregation and pathogenesis in models of Huntington\u2019s disease. <i>Hum. Mol. Genet.<\/i>, <b>23<\/b>, 755\u2013766 (2014).","DOI":"10.1093\/hmg\/ddt466"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Lee HJ, Suk JE, Bae EJ, Lee JH, Paik SR, Lee SJ. Assembly-dependent endocytosis and clearance of extracellular alpha-synuclein. <i>Int. J. Biochem. Cell Biol.<\/i>, <b>40<\/b>, 1835\u20131849 (2008).","DOI":"10.1016\/j.biocel.2008.01.017"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Lee HJ, Suk JE, Bae EJ, Lee SJ. Clearance and deposition of extracellular alpha-synuclein aggregates in microglia. <i>Biochem. Biophys. Res. Commun.<\/i>, <b>372<\/b>, 423\u2013428 (2008).","DOI":"10.1016\/j.bbrc.2008.05.045"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T. Familial Parkinson\u2019s disease gene product, parkin, is a ubiquitin\u2013protein ligase. <i>Nat. Genet.<\/i>, <b>25<\/b>, 302\u2013305 (2000).","DOI":"10.1038\/77060"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Xiong H, Wang D, Chen L, Choo YS, Ma H, Tang C, Xia K, Jiang W, Ronai Z, Zhuang X, Zhang Z. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. <i>J. Clin. Invest.<\/i>, <b>119<\/b>, 650\u2013660 (2009).","DOI":"10.1172\/JCI37617"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Janda E, Isidoro C, Carresi C, Mollace V. Defective autophagy in Parkinson\u2019s disease: role of oxidative stress. <i>Mol. Neurobiol.<\/i>, <b>46<\/b>, 639\u2013661 (2012).","DOI":"10.1007\/s12035-012-8318-1"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Webb JL, Ravikumar B, Atkins J, Skepper JN, Rubinsztein DC. alpha-Synuclein is degraded by both autophagy and the proteasome. <i>J. Biol. Chem.<\/i>, <b>278<\/b>, 25009\u201325013 (2003).","DOI":"10.1074\/jbc.M300227200"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. <i>Science<\/i>, <b>305<\/b>, 1292\u20131295 (2004).","DOI":"10.1126\/science.1101738"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Watanabe Y, Tatebe H, Taguchi K, Endo Y, Tokuda T, Mizuno T, Nakagawa M, Tanaka M. p62\/SQSTM1-dependent autophagy of Lewy body-like alpha-synuclein inclusions. <i>PLoS ONE<\/i>, <b>7<\/b>, e52868 (2012).","DOI":"10.1371\/journal.pone.0052868"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Thomas KJ, McCoy MK, Blackinton J, Beilina A, van der Brug M, Sandebring A, Miller D, Maric D, Cedazo-Minguez A, Cookson MR. DJ-1 acts in parallel with the PINK1\/parkin pathway to control mitochondrial function and autophagy. <i>Hum. Mol. Genet.<\/i>, <b>20<\/b>, 40\u201350 (2011).","DOI":"10.1093\/hmg\/ddq430"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Krebiehl G, Ruckerbauer S, Burbulla LF, Kieper N, Maurer B, Waak J, Wolburg H, Gizatullina Z, Gellerich FN, Woitalla D, Riess O, Kahle PJ, Proikas-Cezanne T, Kruger R. Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson\u2019s disease-associated protein DJ-1. <i>PLoS ONE<\/i>, <b>5<\/b>, e9367 (2010).","DOI":"10.1371\/journal.pone.0009367"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Sun SY, An CN, Pu XP. DJ-1 protein protects dopaminergic neurons against 6-OHDA\/MG-132-induced neurotoxicity in rats. <i>Brain Res. Bull.<\/i>, <b>88<\/b>, 609\u2013616 (2012).","DOI":"10.1016\/j.brainresbull.2012.05.013"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Gao H, Yang W, Qi Z, Lu L, Duan C, Zhao C, Yang H. DJ-1 protects dopaminergic neurons against rotenone-induced apoptosis by enhancing ERK-dependent mitophagy. <i>J. Mol. Biol.<\/i>, <b>423<\/b>, 232\u2013248 (2012).","DOI":"10.1016\/j.jmb.2012.06.034"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Lev N, Barhum Y, Ben-Zur T, Aharony I, Trifonov L, Regev N, Melamed E, Gruzman A, Offen D. A DJ-1 based peptide attenuates dopaminergic degeneration in mice models of Parkinson\u2019s disease <i>via<\/i> enhancing Nrf2. <i>PLoS ONE<\/i>, <b>10<\/b>, e0127549 (2015).","DOI":"10.1371\/journal.pone.0127549"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Miyazaki S, Yanagida T, Nunome K, Ishikawa S, Inden M, Kitamura Y, Nakagawa S, Taira T, Hirota K, Niwa M, Iguchi-Ariga SM, Ariga H. DJ-1-binding compounds prevent oxidative stress-induced cell death and movement defects in Parkinson\u2019s disease model rats. <i>J. Neurochem.<\/i>, <b>105<\/b>, 2418\u20132434 (2008).","DOI":"10.1111\/j.1471-4159.2008.05327.x"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Inden M, Kitamura Y, Takahashi K, Takata K, Ito N, Niwa R, Funayama R, Nishimura K, Taniguchi T, Honda T, Taira T, Ariga H. Protection against dopaminergic neurodegeneration in Parkinson\u2019s disease-model animals by a modulator of the oxidized form of DJ-1, a wild-type of familial Parkinson\u2019s disease-linked PARK7. <i>J. Pharmacol. Sci.<\/i>, <b>117<\/b>, 189\u2013203 (2011).","DOI":"10.1254\/jphs.11151FP"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Kitamura Y, Watanabe S, Taguchi M, Takagi K, Kawata T, Takahashi-Niki K, Yasui H, Maita H, Iguchi-Ariga SM, Ariga H. Neuroprotective effect of a new DJ-1-binding compound against neurodegeneration in Parkinson\u2019s disease and stroke model rats. <i>Mol. Neurodegener.<\/i>, <b>6<\/b>, 48 (2011).","DOI":"10.1186\/1750-1326-6-48"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42) Takahashi-Niki K, Inafune A, Michitani N, Hatakeyama Y, Suzuki K, Sasaki M, Kitamura Y, Niki T, Iguchi-Ariga SM, Ariga H. DJ-1-dependent protective activity of DJ-1-binding compound no. 23 against neuronal cell death in MPTP-treated mouse model of Parkinson\u2019s disease. <i>J. Pharmacol. Sci.<\/i>, <b>127<\/b>, 305\u2013310 (2015).","DOI":"10.1016\/j.jphs.2015.01.010"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43) Kitamura Y, Inden M, Kimoto Y, Takata K, Yanagisawa D, Hijioka M, Ashihara E, Tooyama I, Shimohama S, Ariga H. Effects of a DJ-1-binding compound on spatial learning and memory impairment in a mouse model of alzheimer\u2019s disease. <i>J. Alzheimer\u2019s Dis.<\/i>, <b>55<\/b>, 67\u201372 (2017).","DOI":"10.3233\/JAD-160574"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44) Yamane K, Kitamura Y, Yanagida T, Takata K, Yanagisawa D, Taniguchi T, Taira T, Ariga H. Oxidative neurodegeneration is prevented by UCP0045037, an allosteric modulator for the reduced form of DJ-1, a wild-type of familial Parkinson\u2019s disease-linked PARK7. <i>Int. J. Mol. Sci.<\/i>, <b>10<\/b>, 4789\u20134804 (2009).","DOI":"10.3390\/ijms10114789"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45) Yanagida T, Kitamura Y, Yamane K, Takahashi K, Takata K, Yanagisawa D, Yasui H, Taniguchi T, Taira T, Honda T, Ariga H. Protection against oxidative stress-induced neurodegeneration by a modulator for DJ-1, the wild-type of familial Parkinson\u2019s disease-linked PARK7. <i>J. Pharmacol. 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