{"id":"https://openalex.org/W7221569415","doi":"https://doi.org/10.64898/2026.10.05.756178","title":"Single Cell Proteomics reveals partial uncoupling of the Glycerol-3-Phosphate shuttle to compensate for Electron Transport Chain dysfunction in Alexander Disease GFAP mutations","display_name":"Single Cell Proteomics reveals partial uncoupling of the Glycerol-3-Phosphate shuttle to compensate for Electron Transport Chain dysfunction in Alexander Disease GFAP mutations","publication_year":2026,"publication_date":"2026-10-12","ids":{"openalex":"https://openalex.org/W7221569415","doi":"https://doi.org/10.64898/2026.10.05.756178"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.05.756178","doi":"https://doi.org/10.64898/2026.10.05.756178","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.05.756178","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/12/2026.10.05.756178.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/12/2026.10.05.756178.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5005403518","display_name":"Charlotte A. G. H. van Gelder","orcid":"https://orcid.org/0000-0002-6110-0502","observed_orcids":["https://orcid.org/0000-0002-6110-0502"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Charlotte AGH van Gelder","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-6110-0502","affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050111257","display_name":"Elena Daoutsali","orcid":"https://orcid.org/0000-0003-3133-1104","observed_orcids":["https://orcid.org/0000-0003-3133-1104"]},"institutions":[{"id":"https://openalex.org/I193662353","display_name":"Utrecht University","ror":"https://ror.org/04pp8hn57","country_code":"NL","type":"education","lineage":["https://openalex.org/I193662353"]},{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Elena Daoutsali","raw_affiliation_strings":["Department of Translational Neuroscience, University Medical Centre Utrecht Brain Centre, Utrecht University, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0003-3133-1104","affiliations":[{"raw_affiliation_string":"Department of Translational Neuroscience, University Medical Centre Utrecht Brain Centre, Utrecht University, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I193662353","https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5158502405","display_name":"Yara Attour","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Yara Attour","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5136239369","display_name":"Soufiane El Baghdadi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Soufiane El Baghdadi","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082721949","display_name":"Paula Sobrevals Alcaraz","orcid":"https://orcid.org/0000-0003-0035-7002","observed_orcids":["https://orcid.org/0000-0003-0035-7002"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Paula Sobrevals Alcaraz","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0003-0035-7002","affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056696812","display_name":"Robert M. van Es","orcid":"https://orcid.org/0000-0002-8299-3813","observed_orcids":["https://orcid.org/0000-0002-8299-3813"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Robert M van Es","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-8299-3813","affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5158534375","display_name":"Can Gulersonmez","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Can Gulersonmez","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5017222673","display_name":"Edwin C.A. Stigter","orcid":"https://orcid.org/0000-0001-5970-4668","observed_orcids":["https://orcid.org/0000-0001-5970-4668"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Edwin CA Stigter","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0001-5970-4668","affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5105298865","display_name":"Harmjan R. Vos","orcid":"https://orcid.org/0000-0002-4696-6068","observed_orcids":["https://orcid.org/0000-0002-4696-6068"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Harmjan R Vos","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-4696-6068","affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013180706","display_name":"Elly M. Hol","orcid":"https://orcid.org/0000-0001-5604-2603","observed_orcids":["https://orcid.org/0000-0001-5604-2603"]},"institutions":[{"id":"https://openalex.org/I193662353","display_name":"Utrecht University","ror":"https://ror.org/04pp8hn57","country_code":"NL","type":"education","lineage":["https://openalex.org/I193662353"]},{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Elly M Hol","raw_affiliation_strings":["Department of Translational Neuroscience, University Medical Centre Utrecht Brain Centre, Utrecht University, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0001-5604-2603","affiliations":[{"raw_affiliation_string":"Department of Translational Neuroscience, University Medical Centre Utrecht Brain Centre, Utrecht University, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I193662353","https://openalex.org/I3018483916"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5033711163","display_name":"Boudewijn M.T. Burgering","orcid":"https://orcid.org/0000-0002-4044-9596","observed_orcids":["https://orcid.org/0000-0002-4044-9596"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]},{"id":"https://openalex.org/I4210111138","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28","country_code":"NL","type":"education","lineage":["https://openalex.org/I4210111138"]}],"countries":["NL"],"is_corresponding":true,"raw_author_name":"Boudewijn MT Burgering","raw_affiliation_strings":["Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-4044-9596","affiliations":[{"raw_affiliation_string":"Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]},{"raw_affiliation_string":"Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5033711163"],"corresponding_institution_ids":["https://openalex.org/I3018483916","https://openalex.org/I4210111138"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10301","display_name":"Mitochondrial Function and Pathology","score":0.7401999831199646,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10301","display_name":"Mitochondrial Function and Pathology","score":0.7401999831199646,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11027","display_name":"Metabolism and Genetic Disorders","score":0.19179999828338623,"subfield":{"id":"https://openalex.org/subfields/1308","display_name":"Clinical Biochemistry"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10949","display_name":"Genetic Neurodegenerative Diseases","score":0.006300000008195639,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/alexander-disease","display_name":"Alexander disease","score":1.0},{"id":"https://openalex.org/keywords/glycerol-3-phosphate-shuttle","display_name":"glycerol-3-phosphate shuttle","score":0.9760000109672546},{"id":"https://openalex.org/keywords/electron-transport-chain-dysfunction","display_name":"electron transport chain dysfunction","score":0.9789999723434448},{"id":"https://openalex.org/keywords/astrocyte-metabolism","display_name":"astrocyte metabolism","score":0.7229999899864197},{"id":"https://openalex.org/keywords/glycolytic-reprogramming","display_name":"glycolytic reprogramming","score":0.8949999809265137},{"id":"https://openalex.org/keywords/nad-regeneration","display_name":"NAD+ regeneration","score":0.8140000104904175},{"id":"https://openalex.org/keywords/triglyceride-accumulation","display_name":"triglyceride accumulation","score":0.7609999775886536},{"id":"https://openalex.org/keywords/lipid-droplets","display_name":"lipid droplets","score":0.984000027179718},{"id":"https://openalex.org/keywords/cortical-organoids","display_name":"cortical organoids","score":0.8539999723434448},{"id":"https://openalex.org/keywords/leukodystrophy","display_name":"leukodystrophy","score":0.8450000286102295},{"id":"https://openalex.org/keywords/astrocyte-dysfunction","display_name":"astrocyte dysfunction","score":0.7360000014305115}],"concepts":[{"id":"https://openalex.org/C46111723","wikidata":"https://www.wikidata.org/wiki/Q471857","display_name":"Proteomics","level":3,"score":0.6514999866485596},{"id":"https://openalex.org/C2780495277","wikidata":"https://www.wikidata.org/wiki/Q905442","display_name":"Glial fibrillary acidic protein","level":3,"score":0.6503999829292297},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5831999778747559},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.511900007724762},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.5117999911308289},{"id":"https://openalex.org/C28859421","wikidata":"https://www.wikidata.org/wiki/Q39572","display_name":"Mitochondrion","level":2,"score":0.5091999769210815},{"id":"https://openalex.org/C3020377403","wikidata":"https://www.wikidata.org/wiki/Q211016","display_name":"Respiratory chain","level":3,"score":0.5090000033378601},{"id":"https://openalex.org/C78383274","wikidata":"https://www.wikidata.org/wiki/Q421987","display_name":"Intermediate filament","level":4,"score":0.4745999872684479},{"id":"https://openalex.org/C207583985","wikidata":"https://www.wikidata.org/wiki/Q128723","display_name":"Wild type","level":4,"score":0.41260001063346863},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3758000135421753},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.35690000653266907},{"id":"https://openalex.org/C2775894526","wikidata":"https://www.wikidata.org/wiki/Q2112279","display_name":"Prohibitin","level":3,"score":0.3440000116825104},{"id":"https://openalex.org/C20251656","wikidata":"https://www.wikidata.org/wiki/Q162643","display_name":"Glycolysis","level":3,"score":0.3352000117301941},{"id":"https://openalex.org/C3020761558","wikidata":"https://www.wikidata.org/wiki/Q211016","display_name":"Mitochondrial respiratory chain","level":3,"score":0.33480000495910645},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.3249000012874603},{"id":"https://openalex.org/C98539663","wikidata":"https://www.wikidata.org/wiki/Q220599","display_name":"Cytosol","level":3,"score":0.3174999952316284},{"id":"https://openalex.org/C27740335","wikidata":"https://www.wikidata.org/wiki/Q14878333","display_name":"Proteasome","level":2,"score":0.3172000050544739},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.2985000014305115},{"id":"https://openalex.org/C2776319529","wikidata":"https://www.wikidata.org/wiki/Q3869349","display_name":"NADH dehydrogenase","level":4,"score":0.28839999437332153},{"id":"https://openalex.org/C2992195973","wikidata":"https://www.wikidata.org/wiki/Q33123","display_name":"Protein degradation","level":2,"score":0.2791000008583069},{"id":"https://openalex.org/C2779406938","wikidata":"https://www.wikidata.org/wiki/Q24720289","display_name":"Uncoupling protein","level":4,"score":0.27810001373291016},{"id":"https://openalex.org/C2779926675","wikidata":"https://www.wikidata.org/wiki/Q6943700","display_name":"Mutant protein","level":4,"score":0.27399998903274536},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.2736999988555908},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.2720000147819519},{"id":"https://openalex.org/C57581600","wikidata":"https://www.wikidata.org/wiki/Q2449730","display_name":"Transport protein","level":2,"score":0.2694000005722046}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.05.756178","doi":"https://doi.org/10.64898/2026.10.05.756178","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.05.756178","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/12/2026.10.05.756178.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.10.05.756178","doi":"https://doi.org/10.64898/2026.10.05.756178","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.05.756178","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/12/2026.10.05.756178.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.8560000061988831,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G315159858","display_name":null,"funder_award_id":"NGFOP2201","funder_id":"https://openalex.org/F4320331496","funder_display_name":"Oncode Institute"}],"funders":[{"id":"https://openalex.org/F4320325321","display_name":"Association Europ\u00e9enne contre les Leucodystrophies","ror":"https://ror.org/03wtxje77"},{"id":"https://openalex.org/F4320331496","display_name":"Oncode Institute","ror":"https://ror.org/01n92vv28"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7221569415.pdf","grobid_xml":"https://content.openalex.org/works/W7221569415.grobid-xml"},"referenced_works_count":36,"referenced_works":["https://openalex.org/W1584602900","https://openalex.org/W1881064736","https://openalex.org/W1991238715","https://openalex.org/W1996241541","https://openalex.org/W2039826091","https://openalex.org/W2095408997","https://openalex.org/W2105990535","https://openalex.org/W2160633269","https://openalex.org/W2744284720","https://openalex.org/W2749756316","https://openalex.org/W2773697358","https://openalex.org/W2887980327","https://openalex.org/W2921234630","https://openalex.org/W2956173529","https://openalex.org/W2971506850","https://openalex.org/W2972256582","https://openalex.org/W2985068520","https://openalex.org/W2995442567","https://openalex.org/W3106539179","https://openalex.org/W3113834486","https://openalex.org/W3132240972","https://openalex.org/W3182980201","https://openalex.org/W3214778446","https://openalex.org/W4228999900","https://openalex.org/W4288885783","https://openalex.org/W4292847959","https://openalex.org/W4366484362","https://openalex.org/W4386099975","https://openalex.org/W4398180333","https://openalex.org/W4402750352","https://openalex.org/W4407553827","https://openalex.org/W4408292751","https://openalex.org/W4408848057","https://openalex.org/W4416706601","https://openalex.org/W4416888816","https://openalex.org/W7161236216"],"related_works":["https://openalex.org/W2300608607","https://openalex.org/W3214778446","https://openalex.org/W7223056569","https://openalex.org/W4364860557","https://openalex.org/W4400109238","https://openalex.org/W1910906198","https://openalex.org/W4398180333","https://openalex.org/W7161236216","https://openalex.org/W2972256582","https://openalex.org/W2129962143"],"abstract_inverted_index":{"Abstract":[0],"Alexander":[1],"disease":[2,29,124],"(AxD)":[3],"is":[4,31],"a":[5,77,88,118,279],"rare":[6],"genetic":[7],"leukodystrophy":[8],"caused":[9,52],"by":[10,33,53],"dominant":[11],"mutations":[12],"in":[13,123,174,317],"the":[14,18,34,114,140,200,204,224,248,290],"gene":[15],"coding":[16],"for":[17,120,269],"astrocytic":[19],"intermediate":[20],"filament":[21],"protein":[22],"Glial":[23],"Fibrillary":[24],"Acidic":[25],"Protein":[26],"(GFAP).":[27],"Understanding":[28],"mechanisms":[30],"complicated":[32],"fact":[35],"that":[36,217,286],"mutant":[37,80,128],"GFAP":[38,41,55,75,81,92,108,121,129],"promotes":[39,220],"further":[40],"accumulation,":[42],"making":[43],"it":[44],"difficult":[45],"to":[46,65,233,296],"distinguish":[47],"mutation-specific":[48,100],"effects":[49,98],"from":[50,99,155],"those":[51],"elevated":[54],"levels.":[56],"Here,":[57],"we":[58,95],"performed":[59],"mass":[60],"spectrometry-based":[61],"single":[62],"cell":[63],"proteomics":[64,153],"investigate":[66],"proteomic":[67,115],"alterations":[68],"associated":[69],"with":[70,132,152,186],"increasing":[71],"levels":[72,105],"of":[73,91,106,139,148,162,199,203,210,223,230,282],"wildtype":[74,107],"and":[76,137,145,166,208,212,242,284,299],"common":[78],"AxD-causing":[79],"R239C.":[82],"By":[83,244],"analyzing":[84],"individual":[85],"cells":[86,112,189],"spanning":[87],"broad":[89],"range":[90],"expression":[93],"levels,":[94],"separated":[96],"dosage-dependent":[97],"responses.":[101],"Cells":[102],"expressing":[103],"high":[104],"increasingly":[109],"resembled":[110],"R239C-expressing":[111],"at":[113],"level,":[116],"supporting":[117],"role":[119],"accumulation":[122,209],"pathogenesis.":[125],"In":[126],"contrast,":[127],"specifically":[130],"correlated":[131],"increased":[133,160,194],"mitochondrial":[134,164,294],"antioxidant":[135],"enzymes":[136],"remodeling":[138],"proteasome":[141],"tailored":[142],"toward":[143,239],"ATP-":[144],"ubiquitin-independent":[146],"degradation":[147],"oxidized":[149],"proteins.":[150],"Integration":[151],"data":[154],"patient-derived":[156],"cortical":[157],"organoids":[158],"revealed":[159],"abundance":[161],"nuclear-encoded":[163],"proteins":[165],"respiratory":[167],"chain":[168,182],"assembly":[169],"factors":[170],"without":[171],"corresponding":[172],"changes":[173],"mitochondrially":[175],"encoded":[176],"proteins,":[177],"suggesting":[178],"impaired":[179],"electron":[180],"transport":[181],"(ETC)":[183],"assembly.":[184],"Consistent":[185],"this,":[187],"AxD":[188,255,283],"displayed":[190],"reduced":[191],"oxygen":[192],"consumption,":[193],"glycolytic":[195,259,297],"activity,":[196],"enhanced":[197],"utilization":[198],"cytosolic":[201,231],"part":[202],"glycerol-3-phosphate":[205],"(G3P)":[206],"shuttle,":[207,226],"triacylglycerides":[211],"lipid":[213,240,300],"droplets.":[214],"We":[215],"propose":[216],"ETC":[218,276],"dysfunction":[219,277,295,312],"partial":[221],"uncoupling":[222],"G3P":[225,238,249,291],"allowing":[227],"sustained":[228],"regeneration":[229],"NAD\u207a":[232,246],"support":[234],"glycolysis":[235],"while":[236,261],"diverting":[237],"synthesis":[241],"storage.":[243],"regenerating":[245],"through":[247,289],"shuttle":[250,292],"rather":[251],"than":[252],"lactate":[253,263],"fermentation,":[254],"astrocytes":[256],"may":[257],"sustain":[258],"flux":[260],"preserving":[262],"production,":[264],"an":[265],"important":[266],"metabolic":[267,287],"substrate":[268],"neighboring":[270],"neurons.":[271],"Together,":[272],"our":[273],"findings":[274],"identify":[275],"as":[278],"central":[280],"feature":[281],"suggest":[285],"adaptation":[288],"links":[293],"reprogramming":[298],"accumulation.":[301],"More":[302],"broadly,":[303],"these":[304],"results":[305],"provide":[306],"new":[307],"insight":[308],"into":[309],"how":[310],"astrocyte":[311],"drives":[313],"molecular":[314],"pathways":[315],"implicated":[316],"neurodegeneration.":[318]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-10-13T00:00:00"}
