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2. Study of Alzheimer's disease- and frontotemporal dementia-associated genes in the Cretan Aging Cohort

Author

Mathioudakis, Lambros, Dimovasili, Christina, Bourbouli, Mara, Latsoudis, Helen, Kokosali, Evgenia, Gouna, Garyfallia, Vogiatzi, Emmanouella, Basta, Maria, Kapetanaki, Stefania, Panagiotakis, Simeon, Kanterakis, Alexandros, Boumpas, Dimitrios, Lionis, Christos, Plaitakis, Andreas, Simos, Panagiotis, Vgontzas, Alexandros, Kafetzopoulos, Dimitrios, and Zaganas, Ioannis

Published
2023
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4. High Hereditary Transthyretin-Related Amyloidosis Prevalence in Crete: Genetic Heterogeneity and Distinct Phenotypes

Author

Tzagournissakis, Minas, Foukarakis, Emmanouil, Samonakis, Dimitrios, Tsilimbaris, Miltiadis, Michaelidou, Kleita, Mathioudakis, Lambros, Marinis, Anastasios, Giannakoudakis, Emmanouil, Spanaki, Cleanthe, Skoula, Irene, Erimaki, Sofia, Amoiridis, Georgios, Koutsis, Georgios, Koukouraki, Sofia, Stylianou, Kostas, Plaitakis, Andreas, Mitsias, Panayiotis D., and Zaganas, Ioannis

Published
2022
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7. Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting

Author

Correale, Jorge, Caride, Alejandro, Deri, Norma H., Ballario, Carlos, Broadley, Simon, Kneebone, Chris, Barnett, Michael, Pollard, John, Hodgkinson, Suzanne, Kermode, Allan, Macdonell, Richard, King, John, Butzkueven, Helmut, Lechner-Scott, Jeannette, Saines, Noel, Slee, Mark, Plummer, Chris, Willekens, Barbara, Vanopdenbosch, Ludo, Belachew, Shibeshih, Phan-Ba, Rémy, Delvaux, Valérie, Bissay, Veronique, Debruyne, Jan, Decoo, Danny, Crols, Roeland, Symons, Anoek, Nagels, Guy, Van Pesch, Vincent, Sindic, Christian, Dubois, Benedicte, Medaer, Robert, D'Hooghe, Marie, Guillaume, Daniel, De Smet, Eric, Seeldrayers, Pierrette, Lysandropoulos, Andreas, Vokaer, Mathieu, Geens, Karine, Willems, Christina, Denayer, Pierre, Bureau, Michel, Retif, Cecile, Dupuis, Michel, Bouquiaux, Olivier, Vanderdonckt, Patrick, van Landegem, William, Caekebeke, Jo, Van Ingelghem, Erwin, Peeters, Katelijne, Gerard, Pascale, de Noordhout, Alain Maertens, Desfontaines, Philippe, Urbain, Etienne, Declercq, Inge, Van Wijmeersch, Bart, Vanroose, Erwin, Wibail, Alain, Barthomolé, Emmanuel, Ursell, Melanie, Sweet, Margaret Elizabeth, Howse, David, Jichici, Draga, Shawush, Melad, Namaka, Mike, Traboulsee, Anthony, Hashimoto, Stan, Lo, Raymond, Marchetti, Paul, Lapierre, Yves, Jacques, Francois, MacLean, Gregg, Bhan, Virender, Duquette, Pierre, Stewart, Bradley, Paulseth, John, Kremenchutzky, Marcelo, Vorobeychik, Galina, O'Connor, Paul, Grand'Maison, François, Havrdova, Eva, Meluzinová, Eva, Valis, Martin, Talab, Radomír, Stourac, Pavel, Zapletalová, Olga, Dufek, Michal, Sládková, Vladimíra, Novotna, Alena, Vancurová, Romana, Lhotaková, Libuse, Fiedler, Jiri, Vachova, Marta, Dolezil, David, Stetkarova, Ivana, Rehankova, Adela, Psenica, Petr, Ulehlova, Veronika, Feketova, Sona, Skoda, Ondrej, Färkkilä, Markus, Taneli, Sarasoja, Koivisto, Keijo, Seppä, Juha Matti, Airas, Laura, Elovaara, Irina, Hartikainen, Päivi, Pirttila, Tuula, Louchart, Pierre, Ille, Olivier, Thenint, Jean philippe, Godet, Etienne, Vioud, Marcel Maillet, Colamarino, Renato, Gugenheim, Michel, Grimaud, Jerome, Kopf, Audrey, Billy, Christophe, Huttin, Bernard, Borsotti, Jean paul, Devos, Philippe, Kendjuo, Jean bertin N, Verier, Albert, Chapuis, Stephane, Daluzeau, Nathalie, Angibaud, Gilles, Uriot, Marie-Sylvie Artaud, Ziegler, François, Sellal, François, Moulignier, Antoine, Lavenu, Isabelle, Ismail, Samir, Devy, Richard, Suceveanu, Manuel, Wagner, Marc, Marcel, Sebastien, Derouiche, Faycal, Mostoufizadehghalamfarsa, Sohrab, Delalande, Sophie, Ruggieri, Irene, Van Nieuwenhuyse, Catherine Bossu, Nifle, Chantal, Ondze, Basile, Vasilescu, Carmen Gurau, Vongsouthi, Cyrille, Coustans, Marc, Anne, Olivier, Amevigbe, Josephine, Servan, Jerome, Merienne, Marc, Eck, Philippe, Berroir, Stephane, Busson, Philippe, Barroso, Bruno, Larrieu, Jean-Marc, Giendaj, Catherine Louvet, Malkoun, Imad, Hautecoeur, Patrick, Kwiatkowski, Arnaud, Pouliquen, Andre, Garrigues, Guillaume, Delerue, Olivier, Giraud, Pierric, Gere, Julien, Vaunaize, Jean, Dereeper, Olivier, Seiller, Nicolas, Alsassa, Roger, Vlaicu, Mihaela, Neuville, Veronique, Faucheux, Jean Marc, Bernady, Patricia, Fanjaud, Guy, Viallet, François, Schroeter, Michael, Schlemilch-Paschen, Sylke, Lange, Thomas, Bohr, Kin-Arno, Jendroska, Klaus, Rehkopf, Elisabeth, Bergmann, Arnfin, Kleinschnitz, Christoph, Postert, Thomas, Scholz, Peter, Mauz, Uwe, Stratmann, Hubert, Siefjediers, Veneta, Prantl, Martin, Gehring, Klaus, Zellner, Ruth, Junge, Kathrin, Zellner, Anton, Bacay, Valerina, Schlegel, Eugen, Polzer, Udo, Strauss, Erik, Link, Andreas, Stenzel, Christoph, Freidel, Matthias, Drews, Joachim, Neudert, Christian, Schmitz, Frank, Jaeger, Joachim, Masri, Said, Heuberger, Wolfgang, Trausch, Beate, Ruhnke, Oliver, Scarel, Serena, Bach, Kathlen, Ernst, Michael, Landefeld, Harald, Richter, Nils, Schmidt, Stephan, Krause, Michaela, Dressel, Alezander, Ruth, Roland, Anvari, Kerstin, Gossling, Jens, Schenk, Christoph, Tiedge, Oliver, Bode, Lutz, Eder, Hans-Thomas, Pfeffer, Oliver, Krug, Reinhard, Lassek, Christoph, Fleischer, Eberhard, Meuth, Sven, Klotz, Luisa Hildegard, Peglau, Ines, Kukowski, Borries, Herting, Birgit, Guthke, Kersten, Schierenbeck, Jurgen, Brockmeier, Bernd, Albrecht, Holger, Wuttke, Matthias, Augspach-Hofmann, Regine, Gunther, Stefan, Redbrake, Martin, Franke, Christian, Buchner, Klaus, Gratz, Thomas, Horn, Rolf, Doemges, Frank, Schreiber, Martin, Brosch, Thomas, Horn, Markus, Kittlitz, Matthias, Vulturius, Gabriele, Hinse, Paul, Malessa, Rolf, Wiehler, Stephan, Katsarava, Zaza, Kastrup, Oliver, Kausch, Ulrich, Gullekes, Martin, Fickinger, Markus, Wenzel, Wilhelm, Botefur, Ingolf C., Reifschneider, Gerd, Rauer, Sebastian, Lang, Michael, Harms, Lutz, Eckhardt, Ulrich, Cursiefen, Simone, Linker, Ralf, Angstwurm, Klemens, Haas, Judith, Schuetze, Ivo, Rohm, Eva, Stienker-Fisse, H., Sailer, Michael, Bohringer, Johannes, Maurer, Mathias, Bause, Eberhard, Wersching, Ronald, Dachsel, Reinhardt, Domke, Sylke, Hoffman, Frank, Tackenberg, Bjorn, Roch, Kerstin, Ziebold, Uwe, Kallmann, Boris, Buehler, Bernhard, Faiss, Judith, Faiss, Juergen, Schimrigk, Sebastian, Menges, Christian, Knop, Karl Christian, Koehler, Wolfgang, Siever, Arno, Bufler, Johannes, Gramsl, Georg, Kuhnler, Benedicta, Maschke, Matthias, Stogbauer, Florian, Staude, Lisa, Bethke, Florian, Bitsch, Andreas, Harmjanz, Arndt D., Windsheimer, Jorg, Kieseier, Bernd C., Berkenfeld, Ralf, Tumani, Hayrettin, Kirsch, Michael, Wildemann, Brigitte, Daniels, Regina, Gottwald, Klaus, Elias, Wolfgang-Gerhard, Hoffmann, Olaf, Schwab, Matthias, Pilz, Christopher, Klostermann, Fabian, Hellwig, Kerstin, Berthele, Achim, Bayas, Antonios, Molitor, Daniel, Grothe, Christoph, Wagner, Bert, Karageorgiou, Klimentini, Mitsikostas, Dimosthenis, Kodounis, Antonios, Plaitakis, Andreas, Papadimitriou, Alexandros, Grigoriadis, Nikolaos, Vlaikidis, Nikolaos, Koutlas, Evaggelos, Kyritsis, Athanassios, Papathanassopoulos, Panagiotis, Makris, Nikolaos, Tavernarakis, Antonios, Scarpini, Elio, Montanari, Enrico, Marrosu, Maria Giovanna, Trojano, Maria, Amato, Maria Pia, Rottoli, Mariarosa, Lugaresi, Alessandra, Florio, Ciro, Gasperini, Claudio, Grimaldi, Luigi, Millefiorini, Enrico, Koudriavtseva, Tatiana, Perla, Franco, Mantegazza, Renato, Bertolotto, Antonio, Ghezzi, Angelo, Aguilar, Sandra Quinones, Eisenberg, Eli Skromne, Lopez, Leondardo Llamas, Estudillo, Rocio Marquez, Schrijver, H.M., Wittebol, M.C., Baart, J.C., van Golde, A.E.L., Hengstman, G.J.D., Pop, P.H.M., Bos (Geldrop), M., Medaer, R., Schyns-Soeterboek, Angelique, van der Zwart, A., van Diepen, A.J.H., Verheul, G.A.M., Verhagen, W.I.M., Bos (Helmond), M., Witjes, R.J.G.M., Sinnige, L.G.F., van Munster, E.Th.L., Sanders, E.A.C.M., van Dijl, Ron, Hupperts, R.M.M., Frequin, S.T.F.M., Visser, L.H., Henselmans, J.M.L., Moll, J.W.B., Midgard, Rune, Myhr, Kjell Morten, Edland, Astrid, Telstad, Wenche, Hognestad, Tone, Lund, Christian, Hovdal, Harald, Kamaljit, Kaur, Schepel, Jan, Hogenesch, Roelfien Ida, Schüler, Stephan, Odeh, Francis, Alstadhaug, Karl B., Korsgaard, Olav, Farbu, Elisabeth, Ingvaldsen, Teis Barclay, Soares (SCO), Diana, Rente, José, Guerra, José Manuel Costa, Morganho, Armando, Leitão, António, de Sá, João, Sá, Maria José, Marques, Pinto, Veloso, Mário, Baptista, Miguel Viana, Szilasiová, Jarmila, Copikova-Cudrakova, Daniela, Prochazkova, Lubica, Klimová, Eleonóra, Donath, Vladimir, Brozman, Miroslav, Ramo, Cristina, Ruiz, Domingo Pérez, Hernández, Carmen Calles, Sola, María Eugenia Marzo, Moro, Roberto Suarez, Vidal, Jose Antonio, Rodríguez, Ana Belén Caminero, Ozaeta, Gisela Martin, Nadal, Jordi Batlle, Esquide, Amaya Alvarez de Arcaya, Urtaza, Javier Olascoaga, Martínez-Yélamos, Sergio, Arbizu, Txomin, Torrenta, Lluis Ramio i, Boggild, Mike, Wilson, Martin, Al-Araji, Adnan, Nicholas, Richard, Harrower, Timothy, Redmond, Ian, Wolf, Tilo, Osei-Bonsu, Michael, Mazibrada, Gordon, Rog, David, Cottrell, David, Constantinescu, Cris, Gray, Orla, Belhag, Mohamed, Shehu, Abdullah, Rashid, Waqar, Duddy, Martin, Kappos, Ludwig, Wiendl, Heinz, Spelman, Tim, Pellegrini, Fabio, Chen, Yi, Dong, Qunming, and Koendgen, Harold

Published
2018
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9. Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis

Author

Jen, Joanna C., Chan, Wai-Man, Bosley, Thomas M., Wan, Jijun, Carr, Janai R., Rüb, Udo, Shattuck, David, Salamon, Georges, Kudo, Lili C., Ou, Jing, Kansu, Tülay, al Dhalaan, Hesham, al Zayed, Zayed, MacDonald, David B., Stigsby, Bent, Plaitakis, Andreas, Dretakis, Emmanuel K., Gottlob, Irene, Pieh, Christina, Traboulsi, Elias I., Wang, Qing, Wang, Lejin, Andrews, Caroline, Yamada, Koki, Demer, Joseph L., Karim, Shaheen, Alger, Jeffry R., Geschwind, Daniel H., Deller, Thomas, Sicotte, Nancy L., Nelson, Stanley F., Baloh, Robert W., and Engle, Elizabeth C.

Published
2004

10. Structural Evolution of Primate Glutamate Dehydrogenase 2 as Revealed by In Silico Predictions and Experimentally Determined Structures.

Author

Litso, Ionela, Plaitakis, Andreas, Fadouloglou, Vasiliki E., Providaki, Mary, Kokkinidis, Michael, and Zaganas, Ioannis

Subjects
*GLUTAMATE dehydrogenase, *PRIMATES, *PROTEIN structure prediction, *NEURODEGENERATION, *APES
Abstract

Glutamate dehydrogenase (GDH) interconverts glutamate to a-ketoglutarate and ammonia, interconnecting amino acid and carbohydrate metabolism. In humans, two functional GDH genes, GLUD1 and GLUD2, encode for hGDH1 and hGDH2, respectively. GLUD2 evolved from retrotransposition of the GLUD1 gene in the common ancestor of modern apes. These two isoenzymes are involved in the pathophysiology of human metabolic, neoplastic, and neurodegenerative disorders. The 3D structures of hGDH1 and hGDH2 have been experimentally determined; however, no information is available about the path of GDH2 structure changes during primate evolution. Here, we compare the structures predicted by the AlphaFold Colab method for the GDH2 enzyme of modern apes and their extinct primate ancestors. Also, we analyze the individual effect of amino acid substitutions emerging during primate evolution. Our most important finding is that the predicted structure of GDH2 in the common ancestor of apes was the steppingstone for the structural evolution of primate GDH2s. Two changes with a strong functional impact occurring at the first evolutionary step, Arg443Ser and Gly456Ala, had a destabilizing and stabilizing effect, respectively, making this step the most important one. Subsequently, GDH2 underwent additional modifications that fine-tuned its enzymatic properties to adapt to the functional needs of modern-day primate tissues. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Human GLUD1 and GLUD2 glutamate dehydrogenase localize to mitochondria and endoplasmic reticulum

Author

Mastorodemos, Vasileios, Kotzamani, Dimitra, Zaganas, Ioannis, Arianoglou, Giovanna, Latsoudis, Helen, and Plaitakis, Andreas

Subjects
Endoplasmic reticulum -- Physiological aspects -- Research, Genes -- Physiological aspects -- Research, Mitochondria -- Physiological aspects -- Research, Glutamate dehydrogenase -- Physiological aspects -- Research, Biological sciences, Physiological aspects, Research
Abstract

Mammalian glutamate dehydrogenase (GDH), an enzyme central to glutamate metabolism, is thought to localize to the mitochondrial matrix, although there are also suggestions for the extramitochondrial presence of this protein. Whereas GDH in mammals is encoded by the GLUD1 gene, humans and the great apes have, in addition, a GLUD2 gene showing a distinct expression pattern. The encoded hGDH1 and hGDH2 isoenzymes are highly homologous, but their leader sequences are more divergent. To explore their subcellular targeting, we constructed expression vectors in which hGDH1 or hGDH2 was fused with the enhanced green fluorescent protein (EGFP) and used these to transfect COS 7, HeLa, CHO, HEK293, or neuroblastoma SHSY-5Y cells. Confocal microscopy revealed GDH-EGFP fluorescence in the cytoplasm within coarse structures. Cotransfection experiments using organelle-specific markers revealed that hGDH1 or hGDH2 colocalized with the mitochondrial marker DsRed2-Mito and to a lesser extent with the endoplasmic reticulum marker DsRed2-ER. Western blots detected two GDH-EGFP specific bands: a ~90 kDa band and a ~95 kDa band associated with the mitochondria and the endoplasmic reticulum containing cytosol, respectively. Deletion of the signal sequence, while altering drastically the fluoresce distribution within the cell, prevented GDH from entering the mitochondria, with the ~90 kDa band being retained in the cytosol. In addition, the deletion eliminated the ~95 kDa band from cell lysates, thus confirming that it represents the full-length GDH. Hence, while most of the hGDHs translocate into the mitochondria (a process associated with cleavage of the signal sequence), part of the protein localizes to the endoplasmic reticulum, probably serving additional functions. Key words: glutamate dehydrogenase, leader peptide deletion, subcellular localization, EGFP. La glutamate deshydrogenase de mammifere (GDH), une enzyme centrale du metabolisme du glutamate, est presumee etre localisee dans la matrice mitochondriale meme si sa presence hors de la mitochondrie a aussi ete suggeree. La GDH chez les mammiferes est codee par le gene GLUD1, mais les humains et les grands singes possedent en plus le gene GLUD2 montrant un patron d'expression distinct. Les isoenzymes hGDH1 et hGDH2 sont hautement homologues mais leurs sequences de tete sont plus divergentes. Afin d'explorer leur ciblage subcellulaire, nous avons construit des vecteurs d'expression dans lesquels hGDH1 ou hGDH2 sont fusionnees a la proteine fluorescente EGFP, et nous les avons utilise s pour transfecter des cellules COS 7, HeLa, CHO, HEK293 ou les neuroblastomes SHSY-5Y. La microscopie confocale a revele la presence de la fluorescence de la GDH-EGFP dans le cytoplasme, a l'interieur de structures grossieres. Des experiences de co-transfection avec des marqueurs specifiques d'organelles ont montre que hGDH1 ou hGDH2 sont co-localisees avec le marqueur mitochondrial DsRed2-Mito et, a un degre moindre, avec le marqueur du reticulum endoplasmique DsRed2-ER. L'immunobuvardage a permis de detecter deux bandes specifiques de GDH-EGFP : une bande de ~90 kDa associee a la mitochondrie et une bande de ~95 kDa presente dans le cytosol comprenant le reticulum endoplasmique. La deletion de la sequence signal, en modifiant la distribution cellulaire de la fluorescence de facon importante, empechait la GDH d'entrer dans la mitochondrie, la bande de ~90 kDa etant retenue dans le cytosol. En plus, la deletion a elimine la bande de ~95 kDa des lysats cellulaires, confirmant ainsi qu'elle correspondait a la GDH de pleine longueur. Ainsi, alors que les hGDH sont majoritairement transloquees dans la mitochondrie (un processus associe au clivage de la sequence signal), une partie des proteines se localisent dans le reticulum endoplasmique, jouant probablement d'autres roles. Mots-cles : glutamate deshydrogenase, deletion du peptide de tete, localisation sub-cellulaire, EGFP. [Traduit par la Redaction], Introduction Glutamate dehydrogenase (GDH) (EC 1.4.1.3) catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate and ammonia using NAD+ and (or) NADP+ as cofactors (Smith 1979). In many organisms, the [...]

Published
2009

40. Crystal structure of glutamate dehydrogenase 2, a positively selected novel human enzyme involved in brain biology and cancer pathophysiology

Author

Dimovasili, Christina, primary, Fadouloglou, Vasiliki E., additional, Kefala, Aikaterini, additional, Providaki, Mary, additional, Kotsifaki, Dina, additional, Kanavouras, Konstantinos, additional, Sarrou, Iosifina, additional, Plaitakis, Andreas, additional, Zaganas, Ioannis, additional, and Kokkinidis, Michael, additional

Published
2021
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43. Assessment of Parkinson's disease risk loci in Greece

Author

Kara, Eleanna, Xiromerisiou, Georgia, Spanaki, Cleanthe, Bozi, Maria, Koutsis, Georgios, Panas, Marios, Dardiotis, Efthimios, Ralli, Styliani, Bras, Jose, Letson, Christopher, Edsall, Connor, Pliner, Hannah, Arepalli, Sampath, Kalinderi, Kallirhoe, Fidani, Liana, Bostantjopoulou, Sevasti, Keller, Margaux F., Wood, Nicholas W., Hardy, John, Houlden, Henry, Stefanis, Leonidas, Plaitakis, Andreas, Hernandez, Dena, Hadjigeorgiou, Georgios M., Nalls, Mike A., and Singleton, Andrew B.

Published
2014
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44. A Comparison of Acute Hemorrhagic Stroke Outcomes in 2 Populations: The Crete–Boston Study

Author

Zaganas, Ioannis, Halpin, Amy P., Oleinik, Alexandra, Alegakis, Athanasios, Kotzamani, Dimitra, Zafiris, Spiros, Chlapoutaki, Chryssanthi, Tsimoulis, Dimitris, Giannakoudakis, Emmanouil, Chochlidakis, Nikolaos, Ntailiani, Aikaterini, Valatsou, Christina, Papadaki, Efrosini, Vakis, Antonios, Furie, Karen L., Greenberg, Steven M., and Plaitakis, Andreas

Published
2011
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46. High Prevalence of Transthyretin-Related Amyloidosis in Crete, Greece is Due to Three TTR Pathogenic Variants with Markedly Differing Phenotypic Presentations (3974)

Author

Tzagournissakis, Minas, primary, Foukarakis, Emanouil, additional, Marinis, Anastasios, additional, Mathioudakis, Lambros, additional, Michaelidou, Kleita, additional, Spanaki, Cleanthe, additional, Tsilimbaris, Miltiadis, additional, Plaitakis, Andreas, additional, Mitsias, Panayiotis, additional, and Zaganas, Ioannis, additional

Published
2020
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