Citations 3
Toward actionable interventions in human aging (12th ARDD meeting, 2025)
Dekan, Aleksandr , Lore, Sierra , Yoon, Ye Eun, Sjöholm, Aisyah, Terskikh, Alexey V. , Cuervo, A. M., Georgievskaya, Anastasia , Heinz, Andrea , Adams, Andrew, Tsai, Andy P. , Murray, Anna, Brunet, Anne , Harten, Anne Marije van, Spier, Avi, Shenhar, Ben , Clasen, Berthil, Volbracht, Christiane , Kuppe, Christoph, Cookson, Clive, Banila, Cristiana , Cai, Daisy, Lamming, Dudley W. , Rudnic, Edward, Samra, Elias Bou , Verdin, Eric, Fagagna, Fabrizio d’Adda di, Zmudze, Garri, Jasper, Heinrich, Jang, In Hwa, Lemaitre, J. M., Betts-LaCroix, Joe , Newman, John C. , Kawamura, Kazuto , Schaal, Kennedy Matsagas, Egerton, Kitsu, Fortney, Kristen , Hartenstein, Lars, Niedernhofer, Laura, Katsimpardi, Lida , Melton, Lisa , Ferrucci, Luigi, Sylow, Lykke, Demaria, Marco , Guasch-Ferré, Marta, Borch-Jensen, Martin, Kholin, Maxim, Antonov, Michael, Deleidi, Michela , Mérad, Miriam , Meldal, Morten, Topors, Mourad, Venkatesan, Murali, LeBrasseur, Nathan K., Anzinger, Niklas, Fedichev, Peter O, Kohlhaas, Paul, Mullen, Peter J., Singhal, Priya , Cabo, Raquel, Montgomery, Rusty L. , Rosenzweig-Lipson, Sharon, Jakimov, Sergey, Austad, Steven N. , White, Todd, Zuber, Tom, Rozmaric, Tomaz , Wyss-Coray, Tony, Gladyshev, Vadim N., Sinatti, Vanessa V. C., Wang, Weilan, Harborne, William, Wang, Xing Li, Suh, Yousin , Lee, Y., Koch, Zane, Scheibye-Knudsen, Morten, Niedernhofer, Laura J. , Wyss‐Coray, Tony , Niedernhofer, Laura J , Lamming, Dudley W , Deleidi, Michela , Wyss-Coray, Tony , Bakula, Daniela , Tyshkovskiy, Alexander , Cuervo, Ana M , Seluanov, Andrei , Murray, Anna , Pedersen, Bente Klarlund , Schumacher, Björn , Kennedy, Brian Keith , Suetta, Charlotte , Kuppe, Christoph , Ewald, Collin Y. , Valenzano, Dario Riccardo , Rudnic, Edward M., Teeling, Emma C. , Verdin, Eric , Fang, Evandro Fei , Fagagna, Fabrizio d’Adda di , Galkin, Fedor , Jasper, Heinrich , Jang, In Hwa , Han, Jing‐Dong J. , Justice, Jamie N. , Hoeijmakers, Jan H.J. , Ramos, Javier María Peralta , Lemaı̂tre, Jean-Marc , Aerssens, Jeroen , Belmonte, Juan Carlos Izpisúa , Abdelmohsen, Kotb , Knudsen, Lotte Bjerre , Ferrucci, Luigi , Sylow, Lykke , Schafer, Marissa , Guasch‐Ferré, Marta , Levitt, Michael R. , Meldal, Morten , Fedichev, Peter O. , Mullen, Peter J. , Cabo, Rafael de, Houtkooper, Riekelt H. , Smith, Ryan , Rosenzweig‐Lipson, Sharon, Horvath, Steve , Rando, Thomas A. , White, Todd, Tammela, Tuomas , Gladyshev, Vadim N. , Sinatti, Vanessa V C , Liu, Xiaodong , Suh, Yousin , Koch, Zane , Zhavoronkov, Alex , Scheibye‐Knudsen, Morten
Aging | April 6, 2026 | Volume: 18 | Issue: 1 | Pages: 282-302
C9orf72 Repeat Expansion Induces Metabolic Dysfunction in Human iPSC ‐Derived Microglia and Modulates Glial‐Neuronal Crosstalk
Mearelli, Marika , Hirschberg, Insa, Dubroux, Malvina, Provenzano, Francesca , Rizzuti, Mafalda , Sheth, Udit , Deleidi, Michela , Weissleder, Christin , Sheth, Udit , Deleidi, Michela , Weissleder, Christin , Giachino, Carmela , J., Maria Jose Perez , Ottoboni, Linda , Gendron, Tania F. , Corti, Stefania Paola
Glia | September 1, 2025 | Volume: 74 | Issue: 1 | Pages: No page available
ABSTRACT The C9orf72 hexanucleotide repeat expansion mutation is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but its cell type‐specific effects on energy metabolism and immune pathways remain poorly understood. Using induced pluripotent stem cell (iPSC)‐derived motor neurons, astrocytes, and microglia from C9orf72 patients and their isogenic controls, we investigated metabolic changes at the single‐cell level under basal and inflammatory conditions. Our results showed that microglia are particularly susceptible to metabolic disturbances. While C9orf72 motor neurons exhibited impaired mitochondrial respiration and reduced ATP production, C9orf72 microglia presented pronounced increases in glycolytic activity and oxidative stress, accompanied by the upregulation of the expression of key metabolic enzymes. These metabolic changes in microglia were exacerbated by inflammatory stimuli. To investigate how these changes affect the broader cellular environment, we developed a human iPSC‐derived triculture system comprising motor neurons, astrocytes, and microglia. This model revealed increased metabolic activity in all cell types and highlighted that microglia‐driven metabolic reprogramming in astrocytes contributes to the vulnerability of motor neurons under inflammatory conditions. Our findings highlight the central role of microglia in driving metabolic dysregulation and intercellular crosstalk in ALS pathogenesis and suggest that targeting metabolic pathways in immune cells may provide new therapeutic avenues.
Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson’s Disease
Cooper, Oliver , Seo, Hyemyung , Andrabi, Shaida A. , Guardia‐Laguarta, Cristina , Graziotto, John J. , Sundberg, Maria , McLean, Jesse R., Carrillo‐Reid, Luis , Xie, Zhong , Osborn, Teresia, Hargus, Gunnar , Deleidi, Michela , Lawson, Tristan, Bogetofte, Helle , Pérez-Torres, Eduardo , Clark, Lorraine N. , Moskowitz, Carol, Mazzulli, Joseph R. , Chen, Li , Romero, Norma B. , Jiang, Houbo , Uitti, Ryan J. , Huang, Zhigao, Opala, Grzegorz, Scarffe, Leslie A. , Dawson, Valina L. , Klein, Christine , Ross, Owen A. , Trojanowski, John Q. , Marder, Karen, Przedborski, Serge , Krainc, Dimitri , Dawson, Ted M. , Isacson, Ole , Volpicelli‐Daley, Laura A. , Feng, Jian , Lee, Virginia M.‐Y. , Surmeier, Dalton James , Wszołek, Zbigniew K. , Ross, Owen A , Klein, Christine , Dawson, Valina L , Deleidi, Michela
Science Translational Medicine | July 4, 2012 | Volume: 4 | Issue: 141 | Pages: No page available
Neural cells derived from induced pluripotent stem cells from patients with genetic forms of Parkinson’s disease provide insights into disease pathogenesis.