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44 results on '"Gegg, Matthew E."'

1. Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation

Author

Muñoz-Oreja, Mikel, primary, Sandoval, Abigail, additional, Bruland, Ove, additional, Perez-Rodriguez, Diego, additional, Fernandez-Pelayo, Uxoa, additional, de Arbina, Amaia Lopez, additional, Villar-Fernandez, Marina, additional, Hernández-Eguiazu, Haizea, additional, Hernández, Ixiar, additional, Park, Yohan, additional, Goicoechea, Leire, additional, Pascual-Frías, Nerea, additional, Garcia-Ruiz, Carmen, additional, Fernandez-Checa, Jose, additional, Martí-Carrera, Itxaso, additional, Gil-Bea, Francisco Javier, additional, Hasan, Mazahir T, additional, Gegg, Matthew E, additional, Bredrup, Cecilie, additional, Knappskog, Per-Morten, additional, Gereñu-Lopetegui, Gorka, additional, Varhaug, Kristin N, additional, Bindoff, Laurence A, additional, Spinazzola, Antonella, additional, Yoon, Wan Hee, additional, and Holt, Ian J, additional

Published
2024
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4. Unexpected phenotypic and molecular changes of combined glucocerebrosidase and acid sphingomyelinase deficiency

Author

Keatinge, Marcus, primary, Gegg, Matthew E., additional, Watson, Lisa, additional, Mortiboys, Heather, additional, Li, Nan, additional, Dunning, Mark, additional, Ailani, Deepak, additional, Bui, Hai, additional, van Rens, Astrid, additional, Lefeber, Dirk J., additional, Schapira, Anthony H.V., additional, MacDonald, Ryan B., additional, and Bandmann, Oliver, additional

Published
2023
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15. Contributors

Author

Abeliovich, Hagai, primary, Bernabei, Roberto, additional, Boga, Jose A., additional, Calvani, Riccardo, additional, Chen, Min, additional, Chua, Doreen S.K., additional, Coto-Montes, Ana, additional, Devenish, Rodney J., additional, Galindo, María F., additional, Gegg, Matthew E., additional, Hattori, Nobutaka, additional, Hayat, M.A., additional, Imai, Yuzuru, additional, Inoshita, Tsuyoshi, additional, Jordán, Joaquín, additional, Kanki, Tomotake, additional, Klionsky, Daniel J., additional, Kurihara, Yusuke, additional, Leeuwenburgh, Christiaan, additional, Leung, Wingnang, additional, Lim, Kah-Leong, additional, Lokireddy, Sudarsanareddy, additional, Lorenzi, Maria, additional, Marzetti, Emanuele, additional, Mijaljica, Dalibor, additional, Palau, Xavier Gallart, additional, Prescott, Mark, additional, Reiter, Russel J., additional, Simpson-Lavy, Kobi J., additional, Solesio, Maria E., additional, Sun, Huanhuan, additional, Tieu, Kim, additional, Tolkovsky, Aviva M., additional, Wang, Jin, additional, Wang, Ke, additional, Wang, Lei, additional, Xu, Chuanshan, additional, and Yao, Tso-Pang, additional

Published
2014
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18. Acid Sphingomyelinase Deficiency Normalizes Neuronal Function in GCase Deficiency - Unexpected Biological Rescue Effect of Combined Genetic Risk Factors for Parkinson’s Disease

Author

Keatinge, Marcus, primary, Gegg, Matthew E, additional, Watson, Lisa, additional, Mortiboys, Heather, additional, Bui, Hai, additional, Lefeber, Dirk, additional, Rens, Astrid Van, additional, MacDonald, Ryan, additional, Schapira, Anthony, additional, and Bandmann, Oliver, additional

Published
2020
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21. Loss of acid sphingomyelinase ameliorates disease progression in a vertebrate model of Glucocerebrosidase deficiency

Author

Keatinge, Marcus, Gegg, Matthew E., Watson, Lisa, Mortiboys, Heather, Bui, Hai, van Rens, Astrid, Lefeber, Dirk J., MacDonald, Ryan B., Schapira, Anthony H.V., and Bandmann, Oliver

Abstract

Biallelic glucocerebrosidase (GBA) mutations cause the lysosomal storage disorder Gaucher disease (GD), while heterozygous GBA variants are the strongest and most common genetic risk factor for Parkinson disease (PD). An excessive burden of other lysosomal storage disorder gene variants, in particular for SMPD1 (encoding for acid sphingomyelinase (ASM)) has also been reported in PD. However, it is unclear whether GBA and SMPD1 interact genetically. Zebrafish are an ideal vertebrate system to test for such interactions. We previously characterised a gba1 −/− mutant zebrafish line which displayed key hallmarks of human GD. In this work, we describe the biological interaction of combined glucocerebrosidase (GCase) and ASM deficiency in gba1 −/− ; smpd1 −/− double mutant zebrafish. We observed a marked increase of glucosylceramide, ceramide and other key sphingolipids or their metabolites in gba1 −/− ; smpd1 −/− compared to gba1 −/− or smpd1 −/− zebrafish. Unexpectedly, we observed a marked ameliorating effect of ASM inactivation on behaviour and disease duration in gba1 −/− , resulting in a rescue of the characteristic motor phenotype and improved survival in gba1 −/− ; smpd1 −/− . We identified complete rescue of mitochondrial respiratory chain function with normalisation of lipid peroxidation as the underlying mechanism for the observed rescue effect in gba1 −/− ; smpd1 −/− . Combined ASM knockdown and GCase inhibition in human neuroblastoma SH-SY5Y cells unexpectedly lead to a decrease in monomeric α-synuclein, a key pathogenic protein in PD, which was independent of changes in macroautophagy flux. Our work highlights the importance of investigating the downstream functional consequences of gene-gene interactions in complex interacting pathways to determine any composite risk. Significance statement The additive effect of genetic risk variants on disease incidence is a popular but frequently unproven hypothesis. Variants in the lysosomal disease genes glucocerebrosidase1 ( GBA1 ) and sphingomyelinase ( SMPD1 ) are risk factors for Parkinson’s disease (PD). Zebrafish are ideally suited to study gene-gene interaction. We investigated a genetic interaction between gba1 −/− and smpd1 −/− in gba1 −/− ; smpd1 −/− double-mutant zebrafish and observed an unexpected ameliorating effect of sphingomyelinase deficiency on the gba1 −/− related phenotype with prolonged survival and normalisation of motor behaviour due to rescue of mitochondrial function. Complementing experiments in SH-SY5Y neuroblastoma cells revealed an unexpected lowering of α-synuclein in the presence of combined glucocerebrosidase and sphingomyelinase inhibition. Our study highlights the importance of functional validation for any putative gene-gene interactions.

Published
2019
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25. Autophagic lysosome reformation dysfunction in glucocerebrosidase deficient cells: relevance to Parkinson disease

Author

Magalhaes, Joana, Gegg, Matthew E., Migdalska-Richards, Anna, Doherty, Mary K., Whitfield, Phillip D., and Schapira, Anthony H.V.

Subjects
Neurons, Gaucher Disease, Brain, rab7 GTP-Binding Proteins, Parkinson Disease, Articles, Fibroblasts, Mice, rab GTP-Binding Proteins, Mutation, Autophagy, alpha-Synuclein, Animals, Glucosylceramidase, Humans, Lysosomes
Abstract

Glucocerebrosidase (GBA1) gene mutations increase the risk of Parkinson disease (PD). While the cellular mechanisms associating GBA1 mutations and PD are unknown, loss of the glucocerebrosidase enzyme (GCase) activity, inhibition of autophagy and increased α-synuclein levels have been implicated. Here we show that autophagy lysosomal reformation (ALR) is compromised in cells lacking functional GCase. ALR is a cellular process controlled by mTOR which regenerates functional lysosomes from autolysosomes formed during macroautophagy. A decrease in phopho-S6K levels, a marker of mTOR activity, was observed in models of GCase deficiency, including primary mouse neurons and the PD patient derived fibroblasts with GBA1 mutations, suggesting that ALR is compromised. Importantly Rab7, a GTPase crucial for endosome-lysosome trafficking and ALR, accumulated in GCase deficient cells, supporting the notion that lysosomal recycling is impaired. Recombinant GCase treatment reversed ALR inhibition and lysosomal dysfunction. Moreover, ALR dysfunction was accompanied by impairment of macroautophagy and chaperone-mediated autophagy, increased levels of total and phosphorylated (S129) monomeric α-synuclein, evidence of amyloid oligomers and increased α-synuclein release. Concurrently, we found increased cholesterol and altered glucosylceramide homeostasis which could compromise ALR. We propose that GCase deficiency in PD inhibits lysosomal recycling. Consequently neurons are unable to maintain the pool of mature and functional lysosomes required for the autophagic clearance of α-synuclein, leading to the accumulation and spread of pathogenic α-synuclein species in the brain. Since GCase deficiency and lysosomal dysfunction occur with ageing and sporadic PD pathology, the decrease in lysosomal reformation may be a common feature in PD.

Published
2016

26. Corrigendum to 'DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis.'

Author

Piston, Dominik, Alvarez-Erviti, Lydia, Breuer, Peter, Kaut, Oliver, Larsen, Jan Petter, Bonn, Stefan, Møller, Simon Geir, Wüllner, Ullrich, Schapira, Anthony H V, Gegg, Matthew E, Bansal, Vikas, Gargano, Daniela, Yao, Zhi, Szabadkai, Gyorgy, Odell, Mark, Puno, M Rhyan, Björkblom, Benny, and Maple-Grødem, Jodi

Subjects
ddc:570
Published
2018

27. Unexpected opposing biological effect of genetic risk factors for Parkinson’s disease

Author

Keatinge, Marcus, primary, Gegg, Matthew E., additional, Watson, Lisa, additional, Mortiboys, Heather, additional, Li, Nan, additional, Dunning, Mark, additional, Ailani, Deepak, additional, Bui, Hai, additional, van Rens, Astrid, additional, Lefeber, Dirk J., additional, MacDonald, Ryan B., additional, Schapira, Anthony H.V., additional, and Bandmann, Oliver, additional

Published
2019
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32. Endoplasmic reticulum and lysosomal Ca2+ stores are remodelled in GBA1-linked Parkinson disease patient fibroblasts

Author

Kilpatrick, Bethan S., primary, Magalhaes, Joana, additional, Beavan, Michelle S., additional, McNeill, Alisdair, additional, Gegg, Matthew E., additional, Cleeter, Michael W.J., additional, Bloor-Young, Duncan, additional, Churchill, Grant C., additional, Duchen, Michael R., additional, Schapira, Anthony H., additional, and Patel, Sandip, additional

Published
2016
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35. Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression

Author

Gómez-Sánchez, Rubén, primary, Gegg, Matthew E., additional, Bravo-San Pedro, José M., additional, Niso-Santano, Mireia, additional, Alvarez-Erviti, Lydia, additional, Pizarro-Estrella, Elisa, additional, Gutiérrez-Martín, Yolanda, additional, Alvarez-Barrientos, Alberto, additional, Fuentes, José M., additional, González-Polo, Rosa Ana, additional, and Schapira, Anthony H.V., additional

Published
2014
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37. Guidelines for the use and interpretation of assays for monitoring autophagy

Author

Klionsky, Daniel J., primary, Abdalla, Fabio C., additional, Abeliovich, Hagai, additional, Abraham, Robert T., additional, Acevedo-Arozena, Abraham, additional, Adeli, Khosrow, additional, Agholme, Lotta, additional, Agnello, Maria, additional, Agostinis, Patrizia, additional, Aguirre-Ghiso, Julio A., additional, Ahn, Hyung Jun, additional, Ait-Mohamed, Ouardia, additional, Ait-Si-Ali, Slimane, additional, Akematsu, Takahiko, additional, Akira, Shizuo, additional, Al-Younes, Hesham M., additional, Al-Zeer, Munir A., additional, Albert, Matthew L., additional, Albin, Roger L., additional, Alegre-Abarrategui, Javier, additional, Aleo, Maria Francesca, additional, Alirezaei, Mehrdad, additional, Almasan, Alexandru, additional, Almonte-Becerril, Maylin, additional, Amano, Atsuo, additional, Amaravadi, Ravi K., additional, Amarnath, Shoba, additional, Amer, Amal O., additional, Andrieu-Abadie, Nathalie, additional, Anantharam, Vellareddy, additional, Ann, David K., additional, Anoopkumar-Dukie, Shailendra, additional, Aoki, Hiroshi, additional, Apostolova, Nadezda, additional, Arancia, Giuseppe, additional, Aris, John P., additional, Asanuma, Katsuhiko, additional, Asare, Nana Y.O., additional, Ashida, Hisashi, additional, Askanas, Valerie, additional, Askew, David S., additional, Auberger, Patrick, additional, Baba, Misuzu, additional, Backues, Steven K., additional, Baehrecke, Eric H., additional, Bahr, Ben A., additional, Bai, Xue-Yuan, additional, Bailly, Yannick, additional, Baiocchi, Robert, additional, Baldini, Giulia, additional, Balduini, Walter, additional, Ballabio, Andrea, additional, Bamber, Bruce A., additional, Bampton, Edward T.W., additional, Juhász, Gábor, additional, Bartholomew, Clinton R., additional, Bassham, Diane C., additional, Bast, Robert C., additional, Batoko, Henri, additional, Bay, Boon-Huat, additional, Beau, Isabelle, additional, Béchet, Daniel M., additional, Begley, Thomas J., additional, Behl, Christian, additional, Behrends, Christian, additional, Bekri, Soumeya, additional, Bellaire, Bryan, additional, Bendall, Linda J., additional, Benetti, Luca, additional, Berliocchi, Laura, additional, Bernardi, Henri, additional, Bernassola, Francesca, additional, Besteiro, Sébastien, additional, Bhatia-Kissova, Ingrid, additional, Bi, Xiaoning, additional, Biard-Piechaczyk, Martine, additional, Blum, Janice S., additional, Boise, Lawrence H., additional, Bonaldo, Paolo, additional, Boone, David L., additional, Bornhauser, Beat C., additional, Bortoluci, Karina R., additional, Bossis, Ioannis, additional, Bost, Frédéric, additional, Bourquin, Jean-Pierre, additional, Boya, Patricia, additional, Boyer-Guittaut, Michaël, additional, Bozhkov, Peter V., additional, Brady, Nathan R, additional, Brancolini, Claudio, additional, Brech, Andreas, additional, Brenman, Jay E., additional, Brennand, Ana, additional, Bresnick, Emery H., additional, Brest, Patrick, additional, Bridges, Dave, additional, Bristol, Molly L., additional, Brookes, Paul S., additional, Brown, Eric J., additional, Brumell, John H., additional, Brunetti-Pierri, Nicola, additional, Brunk, Ulf T., additional, Bulman, Dennis E., additional, Bultman, Scott J., additional, Bultynck, Geert, additional, Burbulla, Lena F., additional, Bursch, Wilfried, additional, Butchar, Jonathan P., additional, Buzgariu, Wanda, additional, Bydlowski, Sergio P., additional, Cadwell, Ken, additional, Cahová, Monika, additional, Cai, Dongsheng, additional, Cai, Jiyang, additional, Cai, Qian, additional, Calabretta, Bruno, additional, Calvo-Garrido, Javier, additional, Camougrand, Nadine, additional, Campanella, Michelangelo, additional, Campos-Salinas, Jenny, additional, Candi, Eleonora, additional, Cao, Lizhi, additional, Caplan, Allan B., additional, Carding, Simon R., additional, Cardoso, Sandra M., additional, Carew, Jennifer S., additional, Carlin, Cathleen R., additional, Carmignac, Virginie, additional, Carneiro, Leticia A.M., additional, Carra, Serena, additional, Caruso, Rosario A., additional, Casari, Giorgio, additional, Casas, Caty, additional, Castino, Roberta, additional, Cebollero, Eduardo, additional, Cecconi, Francesco, additional, Celli, Jean, additional, Chaachouay, Hassan, additional, Chae, Han-Jung, additional, Chai, Chee-Yin, additional, Chan, David C., additional, Chan, Edmond Y., additional, Chang, Raymond Chuen-Chung, additional, Che, Chi-Ming, additional, Chen, Ching-Chow, additional, Chen, Guang-Chao, additional, Chen, Guo-Qiang, additional, Chen, Min, additional, Chen, Quan, additional, Chen, Steve S.-L., additional, Chen, WenLi, additional, Chen, Xi, additional, Chen, Xiangmei, additional, Chen, Xiequn, additional, Chen, Ye-Guang, additional, Chen, Yingyu, additional, Chen, Yongqiang, additional, Chen, Yu-Jen, additional, Chen, Zhixiang, additional, Cheng, Alan, additional, Cheng, Christopher H.K., additional, Cheng, Yan, additional, Cheong, Heesun, additional, Cheong, Jae-Ho, additional, Cherry, Sara, additional, Chess-Williams, Russ, additional, Cheung, Zelda H., additional, Chevet, Eric, additional, Chiang, Hui-Ling, additional, Chiarelli, Roberto, additional, Chiba, Tomoki, additional, Chin, Lih-Shen, additional, Chiou, Shih-Hwa, additional, Chisari, Francis V., additional, Cho, Chi Hin, additional, Cho, Dong-Hyung, additional, Choi, Augustine M.K., additional, Choi, DooSeok, additional, Choi, Kyeong Sook, additional, Choi, Mary E., additional, Chouaib, Salem, additional, Choubey, Divaker, additional, Choubey, Vinay, additional, Chu, Charleen T., additional, Chuang, Tsung-Hsien, additional, Chueh, Sheau-Huei, additional, Chun, Taehoon, additional, Chwae, Yong-Joon, additional, Chye, Mee-Len, additional, Ciarcia, Roberto, additional, Ciriolo, Maria R., additional, Clague, Michael J., additional, Clark, Robert S.B., additional, Clarke, Peter G.H., additional, Clarke, Robert, additional, Codogno, Patrice, additional, Coller, Hilary A., additional, Colombo, María I., additional, Comincini, Sergio, additional, Condello, Maria, additional, Condorelli, Fabrizio, additional, Cookson, Mark R., additional, Coombs, Graham H., additional, Coppens, Isabelle, additional, Corbalan, Ramon, additional, Cossart, Pascale, additional, Costelli, Paola, additional, Costes, Safia, additional, Coto-Montes, Ana, additional, Couve, Eduardo, additional, Coxon, Fraser P., additional, Cregg, James M., additional, Crespo, José L., additional, Cronjé, Marianne J., additional, Cuervo, Ana Maria, additional, Cullen, Joseph J., additional, Czaja, Mark J., additional, D'Amelio, Marcello, additional, Darfeuille-Michaud, Arlette, additional, Davids, Lester M., additional, Davies, Faith E., additional, De Felici, Massimo, additional, de Groot, John F., additional, de Haan, Cornelis A.M., additional, De Martino, Luisa, additional, De Milito, Angelo, additional, De Tata, Vincenzo, additional, Debnath, Jayanta, additional, Degterev, Alexei, additional, Dehay, Benjamin, additional, Delbridge, Lea M.D., additional, Demarchi, Francesca, additional, Deng, Yi Zhen, additional, Dengjel, Jörn, additional, Dent, Paul, additional, Denton, Donna, additional, Deretic, Vojo, additional, Desai, Shyamal D., additional, Devenish, Rodney J., additional, Di Gioacchino, Mario, additional, Di Paolo, Gilbert, additional, Di Pietro, Chiara, additional, Díaz-Araya, Guillermo, additional, Díaz-Laviada, Inés, additional, Diaz-Meco, Maria T., additional, Diaz-Nido, Javier, additional, Dikic, Ivan, additional, Dinesh-Kumar, Savithramma P., additional, Ding, Wen-Xing, additional, Distelhorst, Clark W., additional, Diwan, Abhinav, additional, Djavaheri-Mergny, Mojgan, additional, Dokudovskaya, Svetlana, additional, Dong, Zheng, additional, Dorsey, Frank C., additional, Dosenko, Victor, additional, Dowling, James J., additional, Doxsey, Stephen, additional, Dreux, Marlène, additional, Drew, Mark E., additional, Duan, Qiuhong, additional, Duchosal, Michel A., additional, Duff, Karen E., additional, Dugail, Isabelle, additional, Durbeej, Madeleine, additional, Duszenko, Michael, additional, Edelstein, Charles L., additional, Edinger, Aimee L., additional, Egea, Gustavo, additional, Eichinger, Ludwig, additional, Eissa, N. Tony, additional, Ekmekcioglu, Suhendan, additional, El-Deiry, Wafik S., additional, Elazar, Zvulun, additional, Elgendy, Mohamed, additional, Ellerby, Lisa M., additional, Eng, Kai Er, additional, Engelbrecht, Anna-Mart, additional, Engelender, Simone, additional, Erenpreisa, Jekaterina, additional, Escalante, Ricardo, additional, Esclatine, Audrey, additional, Eskelinen, Eeva-Liisa, additional, Espert, Lucile, additional, Espina, Virginia, additional, Fan, Huizhou, additional, Fan, Jia, additional, Fan, Qi-Wen, additional, Fan, Zhen, additional, Fang, Shengyun, additional, Fang, Yongqi, additional, Fanto, Manolis, additional, Fanzani, Alessandro, additional, Farkas, Thomas, additional, Farre, Jean-Claude, additional, Faure, Mathias, additional, Fechheimer, Marcus, additional, Feng, Carl G., additional, Feng, Jian, additional, Feng, Qili, additional, Feng, Youji, additional, Fésüs, László, additional, Feuer, Ralph, additional, Figueiredo-Pereira, Maria E., additional, Fimia, Gian Maria, additional, Fingar, Diane C., additional, Finkbeiner, Steven, additional, Finkel, Toren, additional, Finley, Kim D., additional, Fiorito, Filomena, additional, Fisher, Edward A., additional, Fisher, Paul B., additional, Flajolet, Marc, additional, Florez-McClure, Maria L., additional, Florio, Salvatore, additional, Fon, Edward A., additional, Fornai, Francesco, additional, Fortunato, Franco, additional, Fotedar, Rati, additional, Fowler, Daniel H., additional, Fox, Howard S., additional, Franco, Rodrigo, additional, Frankel, Lisa B., additional, Fransen, Marc, additional, Fuentes, José M., additional, Fueyo, Juan, additional, Fujii, Jun, additional, Fujisaki, Kozo, additional, Fujita, Eriko, additional, Fukuda, Mitsunori, additional, Furukawa, Ruth H., additional, Gaestel, Matthias, additional, Gailly, Philippe, additional, Gajewska, Malgorzata, additional, Galliot, Brigitte, additional, Galy, Vincent, additional, Ganesh, Subramaniam, additional, Ganetzky, Barry, additional, Ganley, Ian G., additional, Gao, Fen-Biao, additional, Gao, George F., additional, Gao, Jinming, additional, Garcia, Lorena, additional, Garcia-Manero, Guillermo, additional, Garcia-Marcos, Mikel, additional, Garmyn, Marjan, additional, Gartel, Andrei L., additional, Gatti, Evelina, additional, Gautel, Mathias, additional, Gawriluk, Thomas R., additional, Gegg, Matthew E., additional, Geng, Jiefei, additional, Germain, Marc, additional, Gestwicki, Jason E., additional, Gewirtz, David A., additional, Ghavami, Saeid, additional, Ghosh, Pradipta, additional, Giammarioli, Anna M., additional, Giatromanolaki, Alexandra N., additional, Gibson, Spencer B., additional, Gilkerson, Robert W., additional, Ginger, Michael L., additional, Ginsberg, Henry N., additional, Golab, Jakub, additional, Goligorsky, Michael S., additional, Golstein, Pierre, additional, Gomez-Manzano, Candelaria, additional, Goncu, Ebru, additional, Gongora, Céline, additional, Gonzalez, Claudio D., additional, Gonzalez, Ramon, additional, González-Estévez, Cristina, additional, González-Polo, Rosa Ana, additional, Gonzalez-Rey, Elena, additional, Gorbunov, Nikolai V., additional, Gorski, Sharon, additional, Goruppi, Sandro, additional, Gottlieb, Roberta A., additional, Gozuacik, Devrim, additional, Granato, Giovanna Elvira, additional, Grant, Gary D., additional, Green, Kim N., additional, Gregorc, Ales, additional, Gros, Frédéric, additional, Grose, Charles, additional, Grunt, Thomas W., additional, Gual, Philippe, additional, Guan, Jun-Lin, additional, Guan, Kun-Liang, additional, Guichard, Sylvie M., additional, Gukovskaya, Anna S., additional, Gukovsky, Ilya, additional, Gunst, Jan, additional, Gustafsson, Åsa B., additional, Halayko, Andrew J., additional, Hale, Amber N., additional, Halonen, Sandra K., additional, Hamasaki, Maho, additional, Han, Feng, additional, Han, Ting, additional, Hancock, Michael K., additional, Hansen, Malene, additional, Harada, Hisashi, additional, Harada, Masaru, additional, Hardt, Stefan E., additional, Harper, J. Wade, additional, Harris, Adrian L., additional, Harris, James, additional, Harris, Steven D., additional, Hashimoto, Makoto, additional, Haspel, Jeffrey A., additional, Hayashi, Shin-ichiro, additional, Hazelhurst, Lori A., additional, He, Congcong, additional, He, You-Wen, additional, Hébert, Marie-Josée, additional, Heidenreich, Kim A., additional, Helfrich, Miep H., additional, Helgason, Gudmundur V., additional, Henske, Elizabeth P., additional, Herman, Brian, additional, Herman, Paul K., additional, Hetz, Claudio, additional, Hilfiker, Sabine, additional, Hill, Joseph A., additional, Hocking, Lynne J., additional, Hofman, Paul, additional, Hofmann, Thomas G., additional, Höhfeld, Jörg, additional, Holyoake, Tessa L., additional, Hong, Ming-Huang, additional, Hood, David A., additional, Hotamisligil, Gökhan S., additional, Houwerzijl, Ewout J., additional, Høyer-Hansen, Maria, additional, Hu, Bingren, additional, Hu, Chien-an A., additional, Hu, Hong-Ming, additional, Hua, Ya, additional, Huang, Canhua, additional, Huang, Ju, additional, Huang, Shengbing, additional, Huang, Wei-Pang, additional, Huber, Tobias B., additional, Huh, Won-Ki, additional, Hung, Tai-Ho, additional, Hupp, Ted R., additional, Hur, Gang Min, additional, Hurley, James B., additional, Hussain, Sabah N.A., additional, Hussey, Patrick J., additional, Hwang, Jung Jin, additional, Hwang, Seungmin, additional, Ichihara, Atsuhiro, additional, Ilkhanizadeh, Shirin, additional, Inoki, Ken, additional, Into, Takeshi, additional, Iovane, Valentina, additional, Iovanna, Juan L., additional, Ip, Nancy Y., additional, Isaka, Yoshitaka, additional, Ishida, Hiroyuki, additional, Isidoro, Ciro, additional, Isobe, Ken-ichi, additional, Iwasaki, Akiko, additional, Izquierdo, Marta, additional, Izumi, Yotaro, additional, Jaakkola, Panu M., additional, Jäättelä, Marja, additional, Jackson, George R., additional, Jackson, William T., additional, Janji, Bassam, additional, Jendrach, Marina, additional, Jeon, Ju-Hong, additional, Jeung, Eui-Bae, additional, Jiang, Hong, additional, Jiang, Hongchi, additional, Jiang, Jean X., additional, Jiang, Ming, additional, Jiang, Qing, additional, Jiang, Xuejun, additional, Jiménez, Alberto, additional, Jin, Meiyan, additional, Jin, Shengkan V., additional, Joe, Cheol O., additional, Johansen, Terje, additional, Johnson, Daniel E., additional, Johnson, Gail V.W., additional, Jones, Nicola L., additional, Joseph, Bertrand, additional, Joseph, Suresh K., additional, Joubert, Annie M., additional, Juillerat-Jeanneret, Lucienne, additional, Jung, Chang Hwa, additional, Jung, Yong-Keun, additional, Kaarniranta, Kai, additional, Kaasik, Allen, additional, Kabuta, Tomohiro, additional, Kadowaki, Motoni, additional, Kågedal, Katarina, additional, Kamada, Yoshiaki, additional, Kaminskyy, Vitaliy O., additional, Kampinga, Harm H., additional, Kanamori, Hiromitsu, additional, Kang, Chanhee, additional, Kang, Khong Bee, additional, Kang, Kwang Il, additional, Kang, Rui, additional, Kang, Yoon-A, additional, Kanki, Tomotake, additional, Kanneganti, Thirumala-Devi, additional, Kanno, Haruo, additional, Kanthasamy, Anumantha G., additional, Kanthasamy, Arthi, additional, Karantza, Vassiliki, additional, Kaushal, Gur P., additional, Kaushik, Susmita, additional, Kawazoe, Yoshinori, additional, Ke, Po-Yuan, additional, Kehrl, John H., additional, Kelekar, Ameeta, additional, Kerkhoff, Claus, additional, Kessel, David H., additional, Khalil, Hany, additional, Kiel, Jan A.K.W., additional, Kiger, Amy A., additional, Kihara, Akio, additional, Kim, Deok Ryong, additional, Kim, Do-Hyung, additional, Kim, Dong-Hou, additional, Kim, Eun-Kyoung, additional, Kim, Hyung-Ryong, additional, Kim, Jae-Sung, additional, Kim, Jeong Hun, additional, Kim, Jin Cheon, additional, Kim, John K., additional, Kim, Peter K., additional, Kim, Seong Who, additional, Kim, Yong-Sun, additional, Kim, Yonghyun, additional, Kimchi, Adi, additional, Kimmelman, Alec C., additional, King, Jason S., additional, Kinsella, Timothy J., additional, Kirkin, Vladimir, additional, Kirshenbaum, Lorrie A., additional, Kitamoto, Katsuhiko, additional, Kitazato, Kaio, additional, Klein, Ludger, additional, Klimecki, Walter T., additional, Klucken, Jochen, additional, Knecht, Erwin, additional, Ko, Ben C.B., additional, Koch, Jan C., additional, Koga, Hiroshi, additional, Koh, Jae-Young, additional, Koh, Young Ho, additional, Koike, Masato, additional, Komatsu, Masaaki, additional, Kominami, Eiki, additional, Kong, Hee Jeong, additional, Kong, Wei-Jia, additional, Korolchuk, Viktor I., additional, Kotake, Yaichiro, additional, Koukourakis, Michael I., additional, Flores, Juan B. Kouri, additional, Kovács, Attila L., additional, Kraft, Claudine, additional, Krainc, Dimitri, additional, Krämer, Helmut, additional, Kretz-Remy, Carole, additional, Krichevsky, Anna M., additional, Kroemer, Guido, additional, Krüger, Rejko, additional, Krut, Oleg, additional, Ktistakis, Nicholas T., additional, Kuan, Chia-Yi, additional, Kucharczyk, Roza, additional, Kumar, Ashok, additional, Kumar, Raj, additional, Kumar, Sharad, additional, Kundu, Mondira, additional, Kung, Hsing-Jien, additional, Kurz, Tino, additional, Kwon, Ho Jeong, additional, La Spada, Albert R., additional, Lafont, Frank, additional, Lamark, Trond, additional, Landry, Jacques, additional, Lane, Jon D., additional, Lapaquette, Pierre, additional, Laporte, Jocelyn F., additional, László, Lajos, additional, Lavandero, Sergio, additional, Lavoie, Josée N., additional, Layfield, Robert, additional, Lazo, Pedro A., additional, Le, Weidong, additional, Le Cam, Laurent, additional, Ledbetter, Daniel J., additional, Lee, Alvin J.X., additional, Lee, Byung-Wan, additional, Lee, Gyun Min, additional, Lee, Jongdae, additional, lee, Ju-hyun, additional, Lee, Michael, additional, Lee, Myung-Shik, additional, Lee, Sug Hyung, additional, Leeuwenburgh, Christiaan, additional, Legembre, Patrick, additional, Legouis, Renaud, additional, Lehmann, Michael, additional, Lei, Huan-Yao, additional, Lei, Qun-Ying, additional, Leib, David A., additional, Leiro, José, additional, Lemasters, John J., additional, Lemoine, Antoinette, additional, Lesniak, Maciej S., additional, Lev, Dina, additional, Levenson, Victor V., additional, Levine, Beth, additional, Levy, Efrat, additional, Li, Faqiang, additional, Li, Jun-Lin, additional, Li, Lian, additional, Li, Sheng, additional, Li, Weijie, additional, Li, Xue-Jun, additional, Li, Yan-Bo, additional, Li, Yi-Ping, additional, Liang, Chengyu, additional, Liang, Qiangrong, additional, Liao, Yung-Feng, additional, Liberski, Pawel P., additional, Lieberman, Andrew, additional, Lim, Hyunjung J., additional, Lim, Kah-Leong, additional, Lim, Kyu, additional, Lin, Chiou-Feng, additional, Lin, Fu-Cheng, additional, Lin, Jian, additional, Lin, Jiandie D., additional, Lin, Kui, additional, Lin, Wan-Wan, additional, Lin, Weei-Chin, additional, Lin, Yi-Ling, additional, Linden, Rafael, additional, Lingor, Paul, additional, Lippincott-Schwartz, Jennifer, additional, Lisanti, Michael P., additional, Liton, Paloma B., additional, Liu, Bo, additional, Liu, Chun-Feng, additional, Liu, Kaiyu, additional, Liu, Leyuan, additional, Liu, Qiong A., additional, Liu, Wei, additional, Liu, Young-Chau, additional, Liu, Yule, additional, Lockshin, Richard A., additional, Lok, Chun-Nam, additional, Lonial, Sagar, additional, Loos, Benjamin, additional, Lopez-Berestein, Gabriel, additional, López-Otín, Carlos, additional, Lossi, Laura, additional, Lotze, Michael T., additional, Low, Peter, additional, Lu, Binfeng, additional, Lu, Bingwei, additional, Lu, Bo, additional, Lu, Zhen, additional, Luciano, Fréderic, additional, Lukacs, Nicholas W., additional, Lund, Anders H., additional, Lynch-Day, Melinda A., additional, Ma, Yong, additional, Macian, Fernando, additional, MacKeigan, Jeff P., additional, Macleod, Kay F., additional, Madeo, Frank, additional, Maiuri, Luigi, additional, Maiuri, Maria Chiara, additional, Malagoli, Davide, additional, Malicdan, May Christine V., additional, Malorni, Walter, additional, Man, Na, additional, Mandelkow, Eva-Maria, additional, Manon, Stephen, additional, Manov, Irena, additional, Mao, Kai, additional, Mao, Xiang, additional, Mao, Zixu, additional, Marambaud, Philippe, additional, Marazziti, Daniela, additional, Marcel, Yves L., additional, Marchbank, Katie, additional, Marchetti, Piero, additional, Marciniak, Stefan J., additional, Marcondes, Mateus, additional, Mardi, Mohsen, additional, Marfe, Gabriella, additional, Mariño, Guillermo, additional, Markaki, Maria, additional, Marten, Mark R., additional, Martin, Seamus J., additional, Martinand-Mari, Camille, additional, Martinet, Wim, additional, Martinez-Vicente, Marta, additional, Masini, Matilde, additional, Matarrese, Paola, additional, Matsuo, Saburo, additional, Matteoni, Raffaele, additional, Mayer, Andreas, additional, Mazure, Nathalie M., additional, McConkey, David J., additional, McConnell, Melanie J., additional, McDermott, Catherine, additional, McDonald, Christine, additional, McInerney, Gerald M., additional, McKenna, Sharon L., additional, McLaughlin, BethAnn, additional, McLean, Pamela J., additional, McMaster, Christopher R., additional, McQuibban, G. Angus, additional, Meijer, Alfred J., additional, Meisler, Miriam H., additional, Meléndez, Alicia, additional, Melia, Thomas J., additional, Melino, Gerry, additional, Mena, Maria A., additional, Menendez, Javier A., additional, Menna-Barreto, Rubem F. S., additional, Menon, Manoj B., additional, Menzies, Fiona M., additional, Mercer, Carol A., additional, Merighi, Adalberto, additional, Merry, Diane E., additional, Meschini, Stefania, additional, Meyer, Christian G., additional, Meyer, Thomas F., additional, Miao, Chao-Yu, additional, Miao, Jun-Ying, additional, Michels, Paul A.M., additional, Michiels, Carine, additional, Mijaljica, Dalibor, additional, Milojkovic, Ana, additional, Minucci, Saverio, additional, Miracco, Clelia, additional, Miranti, Cindy K., additional, Mitroulis, Ioannis, additional, Miyazawa, Keisuke, additional, Mizushima, Noboru, additional, Mograbi, Baharia, additional, Mohseni, Simin, additional, Molero, Xavier, additional, Mollereau, Bertrand, additional, Mollinedo, Faustino, additional, Momoi, Takashi, additional, Monastyrska, Iryna, additional, Monick, Martha M., additional, Monteiro, Mervyn J., additional, Moore, Michael N., additional, Mora, Rodrigo, additional, Moreau, Kevin, additional, Moreira, Paula I., additional, Moriyasu, Yuji, additional, Moscat, Jorge, additional, Mostowy, Serge, additional, Mottram, Jeremy C., additional, Motyl, Tomasz, additional, Moussa, Charbel E.-H., additional, Müller, Sylke, additional, Muller, Sylviane, additional, Münger, Karl, additional, Münz, Christian, additional, Murphy, Leon O., additional, Murphy, Maureen E., additional, Musarò, Antonio, additional, Mysorekar, Indira, additional, Nagata, Eiichiro, additional, Nagata, Kazuhiro, additional, Nahimana, Aimable, additional, Nair, Usha, additional, Nakagawa, Toshiyuki, additional, Nakahira, Kiichi, additional, Nakano, Hiroyasu, additional, Nakatogawa, Hitoshi, additional, Nanjundan, Meera, additional, Naqvi, Naweed I., additional, Narendra, Derek P., additional, Narita, Masashi, additional, Navarro, Miguel, additional, Nawrocki, Steffan T., additional, Nazarko, Taras Y., additional, Nemchenko, Andriy, additional, Netea, Mihai G., additional, Neufeld, Thomas P., additional, Ney, Paul A., additional, Nezis, Ioannis P., additional, Nguyen, Huu Phuc, additional, Nie, Daotai, additional, Nishino, Ichizo, additional, Nislow, Corey, additional, Nixon, Ralph A., additional, Noda, Takeshi, additional, Noegel, Angelika A., additional, Nogalska, Anna, additional, Noguchi, Satoru, additional, Notterpek, Lucia, additional, Novak, Ivana, additional, Nozaki, Tomoyoshi, additional, Nukina, Nobuyuki, additional, Nürnberger, Thorsten, additional, Nyfeler, Beat, additional, Obara, Keisuke, additional, Oberley, Terry D., additional, Oddo, Salvatore, additional, Ogawa, Michinaga, additional, Ohashi, Toya, additional, Okamoto, Koji, additional, Oleinick, Nancy L., additional, Oliver, F. Javier, additional, Olsen, Laura J., additional, Olsson, Stefan, additional, Opota, Onya, additional, Osborne, Timothy F., additional, Ostrander, Gary K., additional, Otsu, Kinya, additional, Ou, Jing-hsiung James, additional, Ouimet, Mireille, additional, Overholtzer, Michael, additional, Ozpolat, Bulent, additional, Paganetti, Paolo, additional, Pagnini, Ugo, additional, Pallet, Nicolas, additional, Palmer, Glen E., additional, Palumbo, Camilla, additional, Pan, Tianhong, additional, Panaretakis, Theocharis, additional, Pandey, Udai Bhan, additional, Papackova, Zuzana, additional, Papassideri, Issidora, additional, Paris, Irmgard, additional, Park, Junsoo, additional, Park, Ohkmae K., additional, Parys, Jan B., additional, Parzych, Katherine R., additional, Patschan, Susann, additional, Patterson, Cam, additional, Pattingre, Sophie, additional, Pawelek, John M., additional, Peng, Jianxin, additional, Perlmutter, David H., additional, Perrotta, Ida, additional, Perry, George, additional, Pervaiz, Shazib, additional, Peter, Matthias, additional, Peters, Godefridus J., additional, Petersen, Morten, additional, Petrovski, Goran, additional, Phang, James M., additional, Piacentini, Mauro, additional, Pierre, Philippe, additional, Pierrefite-Carle, Valérie, additional, Pierron, Gérard, additional, Pinkas-Kramarski, Ronit, additional, Piras, Antonio, additional, Piri, Natik, additional, Platanias, Leonidas C., additional, Pöggeler, Stefanie, additional, Poirot, Marc, additional, Poletti, Angelo, additional, Poüs, Christian, additional, Pozuelo-Rubio, Mercedes, additional, Prætorius-Ibba, Mette, additional, Prasad, Anil, additional, Prescott, Mark, additional, Priault, Muriel, additional, Produit-Zengaffinen, Nathalie, additional, Progulske-Fox, Ann, additional, Proikas-Cezanne, Tassula, additional, Przedborski, Serge, additional, Przyklenk, Karin, additional, Puertollano, Rosa, additional, Puyal, Julien, additional, Qian, Shu-Bing, additional, Qin, Liang, additional, Qin, Zheng-Hong, additional, Quaggin, Susan E., additional, Raben, Nina, additional, Rabinowich, Hannah, additional, Rabkin, Simon W., additional, Rahman, Irfan, additional, Rami, Abdelhaq, additional, Ramm, Georg, additional, Randall, Glenn, additional, Randow, Felix, additional, Rao, V. Ashutosh, additional, Rathmell, Jeffrey C., additional, Ravikumar, Brinda, additional, Ray, Swapan K., additional, Reed, Bruce H., additional, Reed, John C., additional, Reggiori, Fulvio, additional, Régnier-Vigouroux, Anne, additional, Reichert, Andreas S., additional, Reiners, Jr., John J., additional, Reiter, Russel J., additional, Ren, Jun, additional, Revuelta, José L., additional, Rhodes, Christopher J., additional, Ritis, Konstantinos, additional, Rizzo, Elizete, additional, Robbins, Jeffrey, additional, Roberge, Michel, additional, Roca, Hernan, additional, Roccheri, Maria C., additional, Rocchi, Stephane, additional, Rodemann, H. 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Published
2012
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41. Mitochondrial dysfunction associated with glucocerebrosidase deficiency

Author

Gegg, Matthew E. and Schapira, Anthony H.V.

Subjects
Glucocerebrosidase, mitophagy, Neurology, Parkinson's disease, Autophagy, Animals, Humans, Gaucher disease, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Lysosome, Article, lcsh:RC321-571, Mitochondria
Abstract

The lysosomal hydrolase glucocerebrosidase (GCase) is encoded for by the GBA gene. Homozygous GBA mutations cause Gaucher disease (GD), a lysosomal storage disorder. Furthermore, homozygous and heterozygous GBA mutations are numerically the greatest genetic risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. The loss of GCase activity results in impairment of the autophagy‐lysosome pathway (ALP), which is required for the degradation of macromolecules and damaged organelles. Aberrant protein handling of α-synuclein by the ALP occurs in both GD and PD. α-synuclein is the principle component of Lewy bodies, a defining hallmark of PD. Mitochondrial dysfunction is also observed in both GD and PD. In this review we will describe how mitochondria are affected following loss of GCase activity. The pathogenic mechanisms leading to mitochondria dysfunction will also be discussed, focusing on the likely inhibition of the degradation of mitochondria by the ALP, also termed mitophagy. Other pathogenic cellular processes associated with GBA mutations that might contribute, such as the unfolding of GCase in the endoplasmic reticulum, calcium dysregulation and neuroinflammation will also be described. Impairment of the ALP and mitochondria dysfunction are common pathogenic themes between GD and PD and probably explain why GBA mutations increase the risk of developing PD that is very similar to sporadic forms of the disease.

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