[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-468842-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-468842-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","stip1-knockout-mitigates-disease-progression-in-a-synucleinopathy-mouse-model-poster-presentation","STIP1 Knockout Mitigates Disease Progression in a Synucleinopathy Mouse Model - Poster Presentation","","Synucleinopathies such as Parkinson’s disease involve misfolded alpha-synuclein accumulation that drives neurodegeneration, motor dysfunction, and cognitive impairment. Hsp90 normally clears misfolded proteins, but proteostatic stress can create an epichaperome that stabilizes toxic aggregates and accelerates progression. STIP1, a stress-inducible Hsp90 co-chaperone, promotes alpha-synuclein aggregation and epichaperome stabilization. This poster evaluates conditional STIP1 knockout (STIP1Fx/Cre+) using behavioral touchscreen testing and longitudinal neuroimaging to assess disease-modifying effects.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/stip1-knockout-mitigates-disease-progression-in-a-synucleinopathy-mouse-model-poster-presentation/468842/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/stip1-knockout-mitigates-disease-progression-in-a-synucleinopathy-mouse-model-poster-presentation/468842.png","ImageObject",300,407,{"name":42,"@type":43},"Rizky","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-08","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the study’s main objective?","Question",{"text":63,"@type":64},"To determine whether conditional STIP1 knockout alters disease progression in an alpha-synuclein mouse model, using behavioral and neuroimaging measures.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were the STIP1 knockout mice generated and induced?",{"text":68,"@type":64},"M83 transgenic mice expressing human A53T alpha-synuclein were crossed with tamoxifen-inducible CreER mice to produce STIP1Fx/Cre+ and control STIP1Fx/Cre- littermates, then tamoxifen was administered to induce knockout.",{"name":70,"@type":61,"acceptedAnswer":71},"What behavioral and MRI findings support the impact of STIP1 deletion?",{"text":72,"@type":64},"STIP1Fx/Cre+ mice showed a significant genotype-by-day improvement in touchscreen reversal (greater cognitive flexibility). MRI deformation-based morphometry indicated progressive volume increases in multiple regions in Cre+ mice, while Cre- mice showed progressive atrophy.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},468842,1792811079,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":55,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":30,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":110,"preview_page_count":4},962085564807,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","DOI: 10. 1002/alz70856_106526  \nBIOMARKERS  \nPOSTER PRESENTATION  \nNEUROIMAGING  \nSTIP1 Knockout Mitigates Disease Progression in a Synucleinopathy Mouse Model: A Multimodal Behavioral and Neuroimaging Study  \nSara Touj1, 2  Vladislav Novikov3, 4  Medhinee Malvankar 1  Piero Rodriguez 1  Allison Brandt 1  Janice Park 1  Stephanie Tullo2, 5  Daniel Gallino 1   \nGabrielA. Devenyi6  Timothy J Bussey7  Lisa M Saksida3, 7  Ravi S. Menon7  Marco AM Prado7  Mallar M. Chakravarty2, 8  \n1 Douglas Mental Health University Institute, Montreal, QC, Canada  \n2 McGill University, Montreal, QC, Canada  \n3 Robarts Research Institute, London, ON, Canada  \n4 University of Western Ontario, London, ON, Canada  \n5 Computational Brain Anatomy LaboratoryCerebral Imaging Centre-Douglas Mental Health University Institute, Verdun, QC, Canada  \n6 Cerebral Imaging Centre-Douglas Mental Health University Institute, Verdun, QC, Canada  \n7Western University, London, ON, Canada  \n8 Cerebral Imaging Centre, Douglas Mental Health Institute Research Centre, Montreal, QC, Canada  \nCorrespondence  \nSara Touj, Douglas Mental Health University Institute, Montreal, QC, Canada. [Email:](Email: sarra.touj2@mail.mcgill.ca)[ sarra.touj2@mail.mcgill.ca](Email: sarra.touj2@mail.mcgill.ca)  \nAbstract  \nBackground: Synucleinopathies, including Parkinson’s disease (PD), are characterized by misfolded alpha-synuclein (αSyn) accumulation, leading to neurodegeneration, motor dysfunction, and cognitive impairments. Normally, Hsp90 helps clear misfolded proteins, but under proteostatic stress, the chaperone network forms an epichaperome, stabilizing toxic aggregates and worsening disease progression. STIP1 (Stress-Inducible Phosphoprotein 1), a key Hsp90 (Heat Shock Protein 90) co-chaperone, facilitates αSyn aggregation and stabilizes the epichaperome, promoting neurotoxicity. This study investigates conditional STIP1 knockout (STIP1Fx/Cre+) effects on disease progression in an αSyn mouse model, using behavioral and neuroimaging assessments. By examining cognitive outcomes alongside neurodegeneration trajectories, this work aims to determine whether disrupting the epichaperome could serve as a viable strategy for disease modification.  \nMethods: M83 transgenic mice expressing human A53T αSyn were crossed with tamoxifen-inducible CreER mice to generate STIP1Fx/Cre+ and STIP1Fx/Cre − littermates. At 11 weeks, mice received unilateral αSyn preformed fibrils (PFFs) injections into the right dorsal striatum to seed pathology. One week post-surgery, mice were administered tamoxifen for five consecutive days to induceSTIP1knockout. Mice underwent touchscreen-based cognitive assessments. Touchscreen experiments were reproduced at both at McGill and Western University. T1-weighted magnetic resonance images (MRI; 100 μm3 voxels, Bruker 7T) were acquired at -7 and 90 days post-injection (dpi). Deformation-based morphometry (DBM) was used to assess  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.  \nAlzheimer’s Dement. 2025;21(Suppl. 2):e106526.  \n[https://doi.org/10.1002/alz70856_106526](https://doi.org/10.1002/alz70856_106526)  \nwi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz)  \n1of3  \nBIOMARKERS  \nvoxel-wise volumetric changes longitudinally. Linear mixed-effects models analyzed genotype by time interactions for behavioral and MRI data.  \nResults: STIP1Fx/Cre+ mice showed a significant genotype × day interaction (β = 1.94, p = 0.001)in touchscreen reversal, improving faster than STIP1Fx/Cre-mice(Figure1). This suggests enhanced cognitive flexibility, replicated across sites (data shown from McGill site only).  \nMRI DBM analysis revealed that STIP1Fx/Cre+ mice exhibited progressive vol","cbCaiqgmqY9bU9OT","https://ap.wps.com/l/cbCaiqgmqY9bU9OT","pdf",690920,"English","# Background\n# Methods\n# Results\n# Conclusion","[{\"question\":\"What is the study’s main objective?\",\"answer\":\"To determine whether conditional STIP1 knockout alters disease progression in an alpha-synuclein mouse model, using behavioral and neuroimaging measures.\"},{\"question\":\"How were the STIP1 knockout mice generated and induced?\",\"answer\":\"M83 transgenic mice expressing human A53T alpha-synuclein were crossed with tamoxifen-inducible CreER mice to produce STIP1Fx/Cre+ and control STIP1Fx/Cre- littermates, then tamoxifen was administered to induce knockout.\"},{\"question\":\"What behavioral and MRI findings support the impact of STIP1 deletion?\",\"answer\":\"STIP1Fx/Cre+ mice showed a significant genotype-by-day improvement in touchscreen reversal (greater cognitive flexibility). MRI deformation-based morphometry indicated progressive volume increases in multiple regions in Cre+ mice, while Cre- mice showed progressive atrophy.\"}]","STIP1 Knockout Mitigates Disease Progression in a Synucleinopathy Mouse Model - Poster Presentation | PDF",1790774752]