TY - JOUR AU - Solti, K. AU - Kuan, W.-L. AU - Fórizs, B. AU - Kustos, G. AU - Mihály, Judith AU - Varga, Zoltán AU - Herberth, Balázs AU - Moravcsik, É. AU - Kiss, Róbert AU - Kárpáti, Manuéla AU - Mikes, Anna AU - Zhao, Y. AU - Imre, Timea AU - Rochet, J.-C. AU - Aigbirhio, F. AU - Williams-Gray, C.H. AU - Barker, R.A. AU - Tóth, Gergely TI - DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits JF - NEUROBIOLOGY OF DISEASE J2 - NEUROBIOL DIS VL - 134 PY - 2020 SN - 0969-9961 DO - 10.1016/j.nbd.2019.104629 UR - https://m2.mtmt.hu/api/publication/30939202 ID - 30939202 N1 - TTK-NAP B - Drug Discovery Research Group – Neurodegenerative Diseases, Institute of Organic Chemistry, Research Center for Natural Sciences, Budapest, Hungary John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, United Kingdom Cantabio Pharmaceuticals, Palo Alto, CA, United States Institute of Materials and Environmental Chemistry Research Centre for Natural Sciences, Budapest, Hungary Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, United Kingdom MS Metabolomic Research Laboratory, Institute of Organic Chemistry, Research Center for Natural Sciences, Budapest, Hungary Department of Medicinal Chemistry and Molecular Pharmacology and Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, Indiana, United States Export Date: 29 November 2019 CODEN: NUDIE Correspondence Address: Tóth, G.; TTK-NAP B - Drug Discovery Research Group – Neurodegenerative Diseases, Institute of Organic Chemistry, Research Center for Natural SciencesHungary; email: toth.gergely@ttk.hu Chemicals/CAS: alpha synuclein, 154040-18-3; amyloid, 11061-24-8; cysteine, 4371-52-2, 52-89-1, 52-90-4; glyoxalase, 37347-76-5; serine, 56-45-1, 6898-95-9 AB - The loss of native function of the DJ-1 protein has been linked to the development of Parkinson's (PD) and other neurodegenerative diseases. Here we show that DJ-1 aggregates into β-sheet structured soluble and fibrillar aggregates in vitro under physiological conditions and that this process is promoted by the oxidation of its catalytic Cys106 residue. This aggregation resulted in the loss of its native biochemical glyoxalase function and in addition oxidized DJ-1 aggregates were observed to localize within Lewy bodies, neurofibrillary tangles and amyloid plaques in human PD and Alzheimer's (AD) patients' post-mortem brain tissue. These findings suggest that the aggregation of DJ-1 may be a critical player in the development of the pathology of PD and AD and demonstrate that loss of DJ-1 function can happen through DJ-1 aggregation. This could then contribute to AD and PD disease onset and progression. © 2019 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Lőrincz, Péter AU - Takáts, Szabolcs AU - Kárpáti, Manuéla AU - Juhász, Gábor TI - iFly: The eye of the fruit fly as a model to study autophagy and related trafficking pathways. JF - EXPERIMENTAL EYE RESEARCH J2 - EXP EYE RES VL - 144 PY - 2016 SP - 90 EP - 98 PG - 9 SN - 0014-4835 DO - 10.1016/j.exer.2015.06.013 UR - https://m2.mtmt.hu/api/publication/2909896 ID - 2909896 N1 - Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány s. 1/C, Budapest, H-1117, Hungary Momentum Drosophila Autophagy Research Group, Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary Cited By :7 Export Date: 21 September 2022 CODEN: EXERA Correspondence Address: Juhász, G.; Department of Anatomy, Pázmány s. 1/C, Hungary; email: szmrt@elte.hu AB - Autophagy is a process by which eukaryotic cells degrade and recycle their intracellular components within lysosomes. Autophagy is induced by starvation to ensure survival of individual cells, and it has evolved to fulfill numerous additional roles in animals. Autophagy not only provides nutrient supply through breakdown products during starvation, but it is also required for the elimination of damaged or surplus organelles, toxic proteins, aggregates, and pathogens, and is essential for normal organelle turnover. Because of these roles, defects in autophagy have pathological consequences. Here we summarize the current knowledge of autophagy and related trafficking pathways in a convenient model: the compound eye of the fruit fly Drosophila melanogaster. In our review, we present a general introduction of the development and structure of the compound eye. This is followed by a discussion of various neurodegeneration models including retinopathies, with special emphasis on the protective role of autophagy against these diseases. LA - English DB - MTMT ER - TY - JOUR AU - Kim, M AU - Sandford, E AU - Gatica, D AU - Qiu, Y AU - Liu, X AU - Zheng, Y AU - Schulman, BA AU - Xu, J AU - Semple, I AU - Ro, SH AU - Kim, B AU - Mavioglu, RN AU - Tolun, A AU - Jipa, András AU - Takáts, Szabolcs AU - Kárpáti, Manuéla AU - Li, JZ AU - Yapici, Z AU - Juhász, Gábor AU - Lee, JH AU - Klionsky, DJ AU - Burmeister, M TI - Mutation in Atg5 reduces autophagy and leads to ataxia with developmental delay. JF - ELIFE J2 - ELIFE VL - 5 PY - 2016 PG - 18 SN - 2050-084X DO - 10.7554/eLife.12245.001 UR - https://m2.mtmt.hu/api/publication/3010297 ID - 3010297 N1 - Megjegyzés-26698000 N1 Funding details: 087518/Z/08/Z, Wellcome Trust N1 Funding details: 14POST19890021, AHA, American Heart Association N1 Funding details: GM053396, NIH, National Institutes of Health N1 Funding details: GM077053, NIH, National Institutes of Health N1 Funding details: NS078560, NIH, National Institutes of Health N1 Funding details: OD018265, NIH, National Institutes of Health Megjegyzés-26786078 N1 Funding details: 087518/Z/08/Z, Wellcome Trust N1 Funding details: 14POST19890021, AHA, American Heart Association N1 Funding details: GM053396, NIH, National Institutes of Health N1 Funding details: GM077053, NIH, National Institutes of Health N1 Funding details: NS078560, NIH, National Institutes of Health N1 Funding details: OD018265, NIH, National Institutes of Health Megjegyzés-26819436 N1 Funding details: 087518/Z/08/Z, Wellcome Trust N1 Funding details: 14POST19890021, AHA, American Heart Association N1 Funding details: GM053396, NIH, National Institutes of Health N1 Funding details: GM077053, NIH, National Institutes of Health N1 Funding details: NS078560, NIH, National Institutes of Health N1 Funding details: OD018265, NIH, National Institutes of Health AB - Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects' cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health. LA - English DB - MTMT ER - TY - GEN AU - Jipa, András AU - Takáts, Szabolcs AU - Kárpáti, Manuéla AU - Juhász, Gábor TI - Cas9-mediated mutagenesis of core autophagy genes in Drosophila PY - 2016 UR - https://m2.mtmt.hu/api/publication/3083471 ID - 3083471 LA - English DB - MTMT ER - TY - THES AU - Kárpáti, Manuéla TI - A Drosophila Atg gének vizsgálata. a FIP200/Atg17 szerepe az autofágiában TS - a FIP200/Atg17 szerepe az autofágiában PB - Eötvös Loránd Tudományegyetem (ELTE) PY - 2015 SP - 121 DO - 10.15476/ELTE.2014.087 UR - https://m2.mtmt.hu/api/publication/2891895 ID - 2891895 LA - Hungarian DB - MTMT ER - TY - GEN AU - Jipa, András AU - Takáts, Szabolcs AU - Kárpáti, Manuéla AU - Juhasz, G TI - CRISPR/Cas9-mediated mutagenesis of core autophagy genes in Drosophila PY - 2015 UR - https://m2.mtmt.hu/api/publication/3083487 ID - 3083487 LA - English DB - MTMT ER - TY - CONF AU - Jipa, András AU - Takáts, Szabolcs AU - Kárpáti, Manuéla AU - Juhasz, G ED - Róbert, Hohol ED - Zsuzsanna, Heiszler ED - Nóra, Éles-Etele TI - CAS9-MEDIATED MUTAGENESIS OF CORE AUTPHAGY GENES IN DROSOPHILA T2 - Hungarian Molecular Life Sciences 2015 PB - Diamond Congress Kft. C1 - Budapest SN - 9786155270154 PY - 2015 SP - 142 EP - 143 PG - 2 UR - https://m2.mtmt.hu/api/publication/3083495 ID - 3083495 LA - English DB - MTMT ER - TY - BOOK AU - Csikós, György AU - Csizmadia, Tamás AU - Csörgő, Tibor AU - Kárpáti, Manuéla AU - Kis, Viktor AU - Dr. Kovács, Attila AU - Molnár, Kinga AU - Pálfia, Zsolt ED - Lippai, Mónika TI - Állatszervezettani Gyakorlatok ET - 0 PB - ELTE Természettudományi Kar CY - Budapest PY - 2015 SP - 221 UR - https://m2.mtmt.hu/api/publication/3165682 ID - 3165682 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Nagy, Péter AU - Kárpáti, Manuéla AU - Varga, Ágnes AU - Pircs, Karolina Milena AU - Venkei, Z AU - Takáts, Szabolcs AU - Varga, Kata AU - Érdi, Balázs AU - Hegedűs, Krisztina AU - Juhász, Gábor TI - Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila JF - AUTOPHAGY J2 - AUTOPHAGY VL - 10 PY - 2014 IS - 3 SP - 453 EP - 467 PG - 15 SN - 1554-8627 DO - 10.4161/auto.27442 UR - https://m2.mtmt.hu/api/publication/2502657 ID - 2502657 N1 - Megjegyzés-23823594 Megjegyzés-23823728 Megjegyzés-23823755 Megjegyzés-23823799 Megjegyzés-23823938 Megjegyzés-24192952 Megjegyzés-24192958 Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States IMP-Research Institute of Molecular Pathology, Vienna, Austria Cited By :49 Export Date: 4 May 2021 Correspondence Address: Juhász, G.; Department of Anatomy, , Budapest, Hungary; email: szmrt@elte.hu AB - Phagophore-derived autophagosomes deliver cytoplasmic material to lysosomes for degradation and reuse. Autophagy mediated by the incompletely characterized actions of Atg proteins is involved in numerous physiological and pathological settings including stress resistance, immunity, aging, cancer, and neurodegenerative diseases. Here we characterized Atg17/FIP200, the Drosophila ortholog of mammalian RB1CC1/FIP200, a proposed functional equivalent of yeast Atg17. Atg17 disruption inhibits basal, starvation-induced and developmental autophagy, and interferes with the programmed elimination of larval salivary glands and midgut during metamorphosis. Upon starvation, Atg17-positive structures appear at aggregates of the selective cargo Ref(2)P/p62 near lysosomes. This location may be similar to the perivacuolar PAS (phagophore assembly site) described in yeast. Drosophila Atg17 is a member of the Atg1 kinase complex as in mammals, and we showed that it binds to the other subunits including Atg1, Atg13 and Atg101 (C12orf44 in humans, 9430023L20Rik in mice and RGD1359310 in rats). Atg17 is required for the kinase activity of endogenous Atg1 in vivo, as loss of Atg17 prevents the Atg1-dependent shift of endogenous Atg13 to hyperphosphorylated forms, and also blocks punctate Atg1 localization during starvation. Finally, we found that Atg1 overexpression induces autophagy and reduces cell size in Atg17-null mutant fat body cells, and that overexpression of Atg17 promotes endogenous Atg13 phosphorylation and enhances autophagy in an Atg1-dependent manner in the fat body. We propose a model according to which the relative activity of Atg1, estimated by the ratio of hyper- to hypophosphorylated Atg13, contributes to setting low (basal) vs. high (starvation-induced) autophagy levels in Drosophila. LA - English DB - MTMT ER - TY - JOUR AU - Takáts, Szabolcs AU - Pircs, Karolina Milena AU - Nagy, Péter AU - Varga, Ágnes AU - Kárpáti, Manuéla AU - Hegedűs, Krisztina AU - Kramer, H AU - Kovács, Attila Lajos AU - Sass, Miklós AU - Juhász, Gábor TI - Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila JF - MOLECULAR BIOLOGY OF THE CELL J2 - MOL BIOL CELL VL - 25 PY - 2014 IS - 8 SP - 1338 EP - 1354 PG - 17 SN - 1059-1524 DO - 10.1091/mbc.E13-08-0449 UR - https://m2.mtmt.hu/api/publication/2527687 ID - 2527687 N1 - Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pazmany s. 1/C, H-1117 Budapest, Hungary Department of Neuroscience, Department of Cell Biology, University of Texas Southwestern Medical School, Dallas, TX, United States Cited By :138 Export Date: 4 May 2021 CODEN: MBCEE Correspondence Address: Juhász, G.; Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pazmany s. 1/C, H-1117 Budapest, Hungary; email: szmrt@elte.hu LA - English DB - MTMT ER -