[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-444940-105":59,"doc-detail-444940-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","polyserine-domains-are-toxic-and-exacerbate-tau-pathology-in-mice","Polyserine domains are toxic and exacerbate tau pathology in mice","","Polyserine domains are shown to mediate the association between certain nuclear RNA-binding proteins and cytoplasmic tau aggregates in tauopathy models and human patient samples. To test in vivo toxicity and effects on tau pathology, AAV9 delivery was used to express a 42-repeat polyserine protein in wild-type and tau transgenic mice, revealing weight loss, behavioral abnormalities, and Purkinje cell loss. In tau transgenic animals, polyserine further increased phosphorylated and insoluble tau and the seeding capacity of brain extracts, supporting a role in human tauopathy progression.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/polyserine-domains-are-toxic-and-exacerbate-tau-pathology-in-mice/444940/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/polyserine-domains-are-toxic-and-exacerbate-tau-pathology-in-mice/444940.png","ImageObject",300,407,{"name":92,"@type":93},"Mafia Boss","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the study address about polyserine in the brain?","Question",{"text":112,"@type":113},"Whether polyserine expressed in a mammalian brain is toxic and whether it exacerbates tau pathology. The study specifically tests these effects in wild-type and tau transgenic mice.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was polyserine delivered and expressed in the mouse models?",{"text":117,"@type":113},"The researchers used AAV9-mediated delivery to express a 42-repeat polyserine protein in wild-type and tau transgenic mouse models.",{"name":119,"@type":110,"acceptedAnswer":120},"What toxic and disease-related effects were observed after polyserine expression?",{"text":121,"@type":113},"In wild-type animals, polyserine caused reduced weight, behavioral abnormalities, and striking Purkinje cell loss. In tau transgenic mice, it increased phosphorylated and insoluble tau levels and enhanced the seeding capacity of brain extracts.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},444940,1790819480,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41,"preview_page_count":4},962090760730,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","RESEARCH ARTICLE  \nNEUROSCIENCE  \n OPEN ACCESS  \nPolyserine domains are toxic and exacerbate tau pathology in mice  \nMeaghan Van Alstynea, b , Vanessa L. Nguyena, Charles A. Hoefferc, and Roy Parkera, b,d,1 Affiliations are included on p. 11.  \nEdited by Nancy Bonini, University of Pennsylvania, Philadelphia, PA; received October 9, 2025; accepted November 16, 2025  \nPolyserine domains mediate the association of some nuclear RNA-binding proteins with cytoplasmic tau aggregates occurring in tauopathy models and patient samples. In cell lines, polyserine domains mediate colocalization with tau aggregates and promote formation, suggesting that the cytoplasmic mislocalization of polyserine-containing proteins could contribute to human disease. Moreover, polyserine can be produced by repeat-associated non-AUG translation in CAG repeat expansion diseases. However, whether polyserine expressed in a mammalian brain is toxic and/or can exacerbate tau pathology is unknown. We used AAV9-mediated delivery to express a 42-repeat polyserine protein in wild-type and tau transgenic mouse models. We observe that polyserine expression has toxic effects in wild-type animals indicated by reduced weight, behavioral abnormalities, and a striking loss of Purkinje cells. Moreover, in the presence of a pathogenic variant of human tau, polyserine exacerbates disease markers such as phosphorylated and insoluble tau levels and the seeding capacity of brain extracts. These findings demonstrate that polyserine domains can promote tau-mediated pathology ina mouse model and support the hypothesis that polyserine-containing proteins could contribute to the progression of human tauopathies.  \ntau | polyserine | neurodegeneration | tauopathy | repeat expansion  \nThe microtubule-binding protein tau is a key player in several neurodegenerative diseases termed tauopathies ( 1). In disease, tau transitions into an insoluble state, forming intracellular aggregates—a hallmark feature of pathology ( 1) . Multiple factors can contribute to tau pathobiology including posttranslational modifications or disease-associated mutations that promote transition from a microtubule-bound state to an aggregated fibrillar form characteristic of disease (2) . Moreover, in vitro polyanionic cofactors such as RNA accelerate formation offibrillar aggregates (3, 4). However, how potential cellular cofactors affect tau fibrillization in mammalian neurons remains incompletely understood.  \nWe and others have demonstrated that the RNA-binding proteins SRRM2 and Pinin mislocalize to tau aggregates in cell models, animal models and postmortem patient tissue (5, 6) . Long stretches of serine repeats or serine-rich regions drive this association with tau (7). Interestingly, in cellular models, polyserine (polySer)-containing proteins or exogenous polySer form assemblies that are preferred sites oftau aggregation (7) . Further, the levels of polySer-containing proteins correlate with the extent of tau aggregation (7) . However, whether polySer modulates tau aggregation and pathology in animal models is unknown.  \nIn addition to being contained within proteins, polySer proteins can be endogenously expressed in the context of repeat expansion diseases. Specifically, in spinocerebellar ataxia 8 (SCA8) polySer-containing proteins are expressed through repeat-associated non-AUG (RAN) translation of transcripts derived from a CAG expansion translating in the AGC frame (8). In this context, polySer has been shown to accumulate in white matter regions where it coincides with demyelination and degeneration (8) . Moreover, polySer proteins are also expressed from the CAG expansion causal in Huntington’s disease (HD) and are present in striatal regions prominently affected in disease (9, 10). Thus, polySer proteins are expressed across repeat expansion diseases where they may contribute to neurotoxicity. However, the toxic properties of polySer in the mammalian brain remain incompletely understood.  \nHere","cbCaikh7iExdarAF","https://ap.wps.com/l/cbCaikh7iExdarAF","pdf",4761185,12,"English","# Background\n## Tau pathology and cofactors\n## Polyserine and RNA-binding proteins\n# Methods and models\n## AAV9-mediated polyserine expression\n# Key findings\n## Toxic effects in wild-type mice\n## Exacerbation of tau pathology in tau transgenic mice\n# Significance","[{\"question\":\"What question does the study address about polyserine in the brain?\",\"answer\":\"Whether polyserine expressed in a mammalian brain is toxic and whether it exacerbates tau pathology. The study specifically tests these effects in wild-type and tau transgenic mice.\"},{\"question\":\"How was polyserine delivered and expressed in the mouse models?\",\"answer\":\"The researchers used AAV9-mediated delivery to express a 42-repeat polyserine protein in wild-type and tau transgenic mouse models.\"},{\"question\":\"What toxic and disease-related effects were observed after polyserine expression?\",\"answer\":\"In wild-type animals, polyserine caused reduced weight, behavioral abnormalities, and striking Purkinje cell loss. In tau transgenic mice, it increased phosphorylated and insoluble tau levels and enhanced the seeding capacity of brain extracts.\"}]","Polyserine domains are toxic and exacerbate tau pathology in mice | PDF",1790709844]