{"id":"https://openalex.org/W7214448594","doi":"https://doi.org/10.64898/2026.09.21.753131","title":"VCP inhibition prevents cone photoreceptor degeneration in the cpfl1 mouse model of achromatopsia","display_name":"VCP inhibition prevents cone photoreceptor degeneration in the cpfl1 mouse model of achromatopsia","publication_year":2026,"publication_date":"2026-09-26","ids":{"openalex":"https://openalex.org/W7214448594","doi":"https://doi.org/10.64898/2026.09.21.753131"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.21.753131","doi":"https://doi.org/10.64898/2026.09.21.753131","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.21.753131","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/26/2026.09.21.753131.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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"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/2026/09/26/2026.09.21.753131.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5043349278","display_name":"Ana-Cristina Almansa-Garcia","orcid":"https://orcid.org/0009-0002-9973-4444","observed_orcids":["https://orcid.org/0009-0002-9973-4444"]},"institutions":[{"id":"https://openalex.org/I8087733","display_name":"University of T\u00fcbingen","ror":"https://ror.org/03a1kwz48","country_code":"DE","type":"education","lineage":["https://openalex.org/I8087733"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Ana-Cristina Almansa-Garc\u00eda","raw_affiliation_strings":["Graduate Training Centre of Neuroscience, University of T\u00fcbingen, Germany","Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany"],"raw_orcid":"https://orcid.org/0009-0002-9973-4444","affiliations":[{"raw_affiliation_string":"Graduate Training Centre of Neuroscience, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]},{"raw_affiliation_string":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036165715","display_name":"Bowen Cao","orcid":"https://orcid.org/0009-0006-1604-7606","observed_orcids":["https://orcid.org/0009-0006-1604-7606"]},"institutions":[{"id":"https://openalex.org/I8087733","display_name":"University of T\u00fcbingen","ror":"https://ror.org/03a1kwz48","country_code":"DE","type":"education","lineage":["https://openalex.org/I8087733"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Bowen Cao","raw_affiliation_strings":["Graduate Training Centre of Neuroscience, University of T\u00fcbingen, Germany","Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Graduate Training Centre of Neuroscience, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]},{"raw_affiliation_string":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5118628527","display_name":"Anne-Sophie Petremann-Dum\u00e9","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I8087733","display_name":"University of T\u00fcbingen","ror":"https://ror.org/03a1kwz48","country_code":"DE","type":"education","lineage":["https://openalex.org/I8087733"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Anne-Sophie Petremann-Dum\u00e9","raw_affiliation_strings":["Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5080318650","display_name":"Ellen Kilger","orcid":"https://orcid.org/0009-0002-2106-5906","observed_orcids":["https://orcid.org/0009-0002-2106-5906"]},"institutions":[{"id":"https://openalex.org/I8087733","display_name":"University of T\u00fcbingen","ror":"https://ror.org/03a1kwz48","country_code":"DE","type":"education","lineage":["https://openalex.org/I8087733"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Ellen Kilger","raw_affiliation_strings":["Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072948197","display_name":"Sylvia Bolz","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I8087733","display_name":"University of T\u00fcbingen","ror":"https://ror.org/03a1kwz48","country_code":"DE","type":"education","lineage":["https://openalex.org/I8087733"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Sylvie Bolz","raw_affiliation_strings":["Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5021919197","display_name":"Marius Ueffing","orcid":"https://orcid.org/0000-0003-2209-2113","observed_orcids":["https://orcid.org/0000-0003-2209-2113"]},"institutions":[{"id":"https://openalex.org/I8087733","display_name":"University of T\u00fcbingen","ror":"https://ror.org/03a1kwz48","country_code":"DE","type":"education","lineage":["https://openalex.org/I8087733"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Marius Ueffing","raw_affiliation_strings":["Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5053204551","display_name":"Blanca Arango\u2010Gonz\u00e1lez","orcid":"https://orcid.org/0000-0002-9045-182X","observed_orcids":["https://orcid.org/0000-0002-9045-182X"]},"institutions":[{"id":"https://openalex.org/I8087733","display_name":"University of T\u00fcbingen","ror":"https://ror.org/03a1kwz48","country_code":"DE","type":"education","lineage":["https://openalex.org/I8087733"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Blanca Arango-Gonzalez","raw_affiliation_strings":["Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany"],"raw_orcid":"https://orcid.org/0000-0002-9045-182X","affiliations":[{"raw_affiliation_string":"Institute for Ophthalmic Research, Centre for Ophthalmology, University of T\u00fcbingen, Germany","institution_ids":["https://openalex.org/I8087733"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5053204551"],"corresponding_institution_ids":["https://openalex.org/I8087733"],"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/T10691","display_name":"Retinal Development and Disorders","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2731","display_name":"Ophthalmology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10691","display_name":"Retinal Development and Disorders","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2731","display_name":"Ophthalmology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11150","display_name":"Endoplasmic Reticulum Stress and Disease","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell 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/T10170","display_name":"Retinal Diseases and Treatments","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2731","display_name":"Ophthalmology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/achromatopsia","display_name":"achromatopsia","score":0.9919999837875366},{"id":"https://openalex.org/keywords/cone-photoreceptor-degeneration","display_name":"cone photoreceptor degeneration","score":0.8830000162124634},{"id":"https://openalex.org/keywords/valosin-containing-protein","display_name":"VCP","score":0.9599999785423279},{"id":"https://openalex.org/keywords/endoplasmic-reticulum-stress","display_name":"endoplasmic reticulum stress","score":0.9380000233650208},{"id":"https://openalex.org/keywords/unfolded-protein-response","display_name":"unfolded protein response","score":0.9929999709129333},{"id":"https://openalex.org/keywords/phototransduction","display_name":"phototransduction","score":0.7760000228881836}],"concepts":[{"id":"https://openalex.org/C2777906962","wikidata":"https://www.wikidata.org/wiki/Q432396","display_name":"Achromatopsia","level":3,"score":0.8604999780654907},{"id":"https://openalex.org/C131667965","wikidata":"https://www.wikidata.org/wiki/Q445081","display_name":"Visual phototransduction","level":3,"score":0.8539999723434448},{"id":"https://openalex.org/C30028475","wikidata":"https://www.wikidata.org/wiki/Q24785022","display_name":"Opsin","level":4,"score":0.6941999793052673},{"id":"https://openalex.org/C2781040256","wikidata":"https://www.wikidata.org/wiki/Q7316761","display_name":"Retinal degeneration","level":3,"score":0.691100001335144},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.6571999788284302},{"id":"https://openalex.org/C202033177","wikidata":"https://www.wikidata.org/wiki/Q423107","display_name":"Rhodopsin","level":3,"score":0.574400007724762},{"id":"https://openalex.org/C2777093970","wikidata":"https://www.wikidata.org/wiki/Q169342","display_name":"Retina","level":2,"score":0.5703999996185303},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5550000071525574},{"id":"https://openalex.org/C158617107","wikidata":"https://www.wikidata.org/wiki/Q79927","display_name":"Endoplasmic reticulum","level":2,"score":0.5044000148773193},{"id":"https://openalex.org/C2780916184","wikidata":"https://www.wikidata.org/wiki/Q748049","display_name":"Photoreceptor cell","level":3,"score":0.44510000944137573},{"id":"https://openalex.org/C2779113765","wikidata":"https://www.wikidata.org/wiki/Q681562","display_name":"Electroretinography","level":3,"score":0.444599986076355},{"id":"https://openalex.org/C2780827179","wikidata":"https://www.wikidata.org/wiki/Q422001","display_name":"Retinal","level":2,"score":0.4023999869823456},{"id":"https://openalex.org/C2781114197","wikidata":"https://www.wikidata.org/wiki/Q847057","display_name":"Retinitis pigmentosa","level":3,"score":0.37959998846054077},{"id":"https://openalex.org/C139447449","wikidata":"https://www.wikidata.org/wiki/Q14633900","display_name":"Unfolded protein response","level":3,"score":0.3391000032424927},{"id":"https://openalex.org/C6929976","wikidata":"https://www.wikidata.org/wiki/Q3771881","display_name":"Regulator","level":3,"score":0.3287999927997589},{"id":"https://openalex.org/C2778231335","wikidata":"https://www.wikidata.org/wiki/Q4113701","display_name":"Outer nuclear layer","level":3,"score":0.32199999690055847},{"id":"https://openalex.org/C171056886","wikidata":"https://www.wikidata.org/wiki/Q193119","display_name":"Regeneration (biology)","level":2,"score":0.28600001335144043},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.2849000096321106},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.28040000796318054},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.27889999747276306},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.26840001344680786},{"id":"https://openalex.org/C149574991","wikidata":"https://www.wikidata.org/wiki/Q420428","display_name":"Transducin","level":4,"score":0.26499998569488525}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.21.753131","doi":"https://doi.org/10.64898/2026.09.21.753131","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.21.753131","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/26/2026.09.21.753131.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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.21.753131","doi":"https://doi.org/10.64898/2026.09.21.753131","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.21.753131","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/26/2026.09.21.753131.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":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.9476000070571899,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7214448594.pdf","grobid_xml":"https://content.openalex.org/works/W7214448594.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4205366873","https://openalex.org/W2806377196","https://openalex.org/W3098674736","https://openalex.org/W2996483235","https://openalex.org/W7119652344","https://openalex.org/W2747200352","https://openalex.org/W3117398331","https://openalex.org/W2061331516","https://openalex.org/W1965566484","https://openalex.org/W4411639420"],"abstract_inverted_index":{"Abstract":[0],"Achromatopsia":[1],"(ACHM)":[2],"is":[3],"a":[4,67,82,210],"rare":[5],"autosomal":[6],"recessive":[7],"retinal":[8,112],"disorder":[9],"characterized":[10],"by":[11,135,191],"absent":[12],"cone":[13,30,92,97,147,151,195,216],"photoreceptor":[14,98],"function":[15,99],"from":[16,114],"early":[17],"life,":[18],"leading":[19],"to":[20,156,165],"severe":[21],"visual":[22],"impairment.":[23],"Mutations":[24],"in":[25,28,35,94,161,170,202,218],"genes":[26],"involved":[27],"the":[29,53,95,120,157,203],"phototransduction":[31],"cascade":[32],"frequently":[33],"result":[34],"elevated":[36],"cyclic":[37],"guanosine":[38],"monophosphate":[39],"(cGMP)":[40],"levels":[41],"and":[42,52,87,131,139,149,154,197],"activation":[43],"of":[44,78,85,107,111],"stress":[45,51],"pathways,":[46],"including":[47],"endoplasmic":[48],"reticulum":[49],"(ER)":[50],"unfolded":[54],"protein":[55,80,88],"response.":[56],"Targeting":[57,206],"common":[58],"downstream":[59],"mechanisms":[60],"rather":[61],"than":[62],"individual":[63],"mutations":[64],"may":[65,208],"provide":[66],"broadly":[68],"applicable":[69],"therapeutic":[70,212],"strategy.":[71],"Here,":[72],"we":[73],"investigated":[74],"whether":[75],"pharmacological":[76],"inhibition":[77,178,190],"valosin-containing":[79],"(VCP),":[81],"key":[83],"regulator":[84],"ER":[86],"homeostasis,":[89],"can":[90],"prevent":[91],"degeneration":[93],"spontaneous":[96],"loss":[100],"1":[101],"(":[102],"cpfl1":[103,115,162,204],")":[104],"mouse":[105],"model":[106],"ACHM.":[108,219],"Organotypic":[109],"culture":[110],"explants":[113,163],"mice":[116],"were":[117,133],"treated":[118],"with":[119],"selective":[121],"VCP":[122,177,189,207],"inhibitor":[123],"ML240.":[124],"Cone":[125],"survival,":[126],"cell":[127],"death,":[128],"opsin":[129,152],"expression":[130,153],"localization":[132],"assessed":[134],"TUNEL":[136],"assay,":[137],"immunohistochemistry,":[138],"quantitative":[140],"image":[141],"analysis.":[142],"ML240":[143,192],"treatment":[144],"significantly":[145],"increased":[146],"density":[148],"improved":[150],"trafficking":[155,169],"outer":[158],"segments":[159],"(OSs)":[160],"compared":[164],"controls.":[166],"Importantly,":[167],"rhodopsin":[168],"rod":[171,183],"photoreceptors":[172,196],"was":[173],"unaffected,":[174],"indicating":[175],"that":[176,188],"did":[179],"not":[180],"impair":[181],"normal":[182],"phototransduction.":[184],"These":[185],"findings":[186],"demonstrate":[187],"effectively":[193],"preserves":[194],"improves":[198],"cone-specific":[199],"functional":[200],"markers":[201],"model.":[205],"represent":[209],"mutation-independent":[211],"strategy":[213],"for":[214],"preventing":[215],"death":[217]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-09-27T00:00:00"}
