{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kury S"],"funding":["U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)","Deutsche Forschungsgemeinschaft (German Research Foundation)","NIMH NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)","AXA Research Fund (Le Fonds AXA pour la Recherche)","Centre Hospitalier Universitaire de Nantes (CHU de Nantes)","NINDS NIH HHS","Agence Nationale de la Recherche (French National Research Agency)","European Cooperation in Science and Technology (COST)","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["10545"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12658096"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progeni"],"journal":["Nature communications"],"pubmed_title":["Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies."],"pmcid":["PMC12658096"],"funding_grant_id":["ANR-10- IAIHU-06","K23 NS119666","K23NS119666","SPP 2453 KR1915/11-1","ANR-21-CE17-0005","TND-UPS","PROG/09/72-03","ProteoCure CA20113","ANR-22-RAR4-0001-01","RC22_0020","82201314","R01 MH101221","R01MH101221","RTG PRO 2719"],"pubmed_authors":["Garganis K","Poirier L","Babikyan D","Turner TN","Saif HA","Hajianpour MJ","Laumonnier F","Ganetzky RD","Malicdan MCV","Ebstein F","Tuttle A","Wiame E","Thompson ML","Bigou S","Muraresku CC","Florenceau L","Bosc-Rosati A","Boothe E","Steindl K","Wolfgramm S","Meiler J","Wegler M","Sznajer Y","Isidor B","Levy J","Hildebrand PW","Vignard V","Potocki L","Deb W","Oloude M","Studencka-Turski M","Pandya A","Timberlake AT","Pappas J","Sorlin A","Kamphausen SB","Dauber A","Bothe V","Stanton JE","Smith RA","Papendorf JJ","de Konink C","Bernier RA","Marsac S","Hammer E","Ziegler A","Verres Y","Ortiz D","Striesow J","Fabie NAV","Rabin R","Begtrup A","Costain G","Wolfe L","Krawitz PM","De Bie I","Jenkins L","Adams DR","Bryson LJ","Torti E","Poschmann J","Langas SJ","Abou Jamra R","Kruger E","Gomez-Andres D","Volker U","McWalter K","Ververi A","Droit A","Sedlacek Z","Grabrucker AM","Baker J","Wende K","Dangoumau A","Cogne B","Sabir A","Hsieh TC","McDonald K","Marcoux J","Tizzano EF","Golnik R","Ivanovski I","Rio M","Abdulrazak A","Hancarova M","Wang T","Busch LM","Dies KA","Elgersma Y","Wentzensen IM","Besnard T","Chun-Hui Tsai A","Gooch C","Bousquet MP","Li C","Vitobello A","Monaghan KG","Bezieau S","Rauch A","Harel T","van Gassen KLI","Most V","Codina-Sola M","Lambropoulos A","Scott-Boyer MP","Philippe C","Nestler B","Hoffman TL","Houdayer C","Volker-Touw CMLN","Bolduc FV","Prendergast D","Bray L","Pavlidou E","Jobling RK","Toker O","Rosenfeld JA","de Pagter MS","Ripoll C","Olinger E","Cuinat S","Oegema R","Kovak K","King K","Bonneau D","D'Agostino MD","Swanson LC","Cueto-Gonzalez AM","Lessard MK","Roux-Dalvai F","Rosenfelt C","Mullegama SV","Cleary E","Kury S","Costin C","Hamilton MJ","Hajdukowicz AM","Genevieve D","van Woerden GM","Beck DB","Schroeder MC","Srivastava S","Forster C","Lim D","Weber S","Eichler EE","Niyazov D","McRae AM","Thiel FG"],"additional_accession":[]},"is_claimable":false,"name":"Investigating the neuronal role of the proteasomal ATPase subunit gene PSMC5 in neurodevelopmental proteasomopathies.","description":"Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5, encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila, we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progeni","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-07-15T09:10:48.251Z","creation":"2026-07-02T03:08:58.205Z"},"accession":"S-EPMC12658096","cross_references":{"pubmed":["41298377"],"doi":["10.1038/s41467-025-65556-8"]}}