{"id":"https://openalex.org/W2941934997","doi":null,"title":"A popular antidepressant drug and its metabolite induce toxicity via beta-amyloid and a serotonin transporter-dependent mechanism","display_name":"A popular antidepressant drug and its metabolite induce toxicity via beta-amyloid and a serotonin transporter-dependent mechanism","publication_year":2019,"publication_date":"2019-04-01","ids":{"openalex":"https://openalex.org/W2941934997","mag":"2941934997"},"language":"en","primary_location":{"id":"pmh:oai:harvest.usask.ca:10388/11773","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/10388/11773","pdf_url":"https://harvest.usask.ca/bitstreams/bb11d2be-4b4e-47f2-ae36-59159613e027/download","source":{"id":"https://openalex.org/S7407063267","display_name":"HARVEST (University of Saskatchewan)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://harvest.usask.ca/bitstreams/bb11d2be-4b4e-47f2-ae36-59159613e027/download","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5082194065","display_name":"Kaeli J. Knudsen","orcid":"https://orcid.org/0000-0002-3760-8939","observed_orcids":["https://orcid.org/0000-0002-3760-8939"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Kaeli Jean Knudsen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5082194065"],"corresponding_institution_ids":[],"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/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9994999766349792,"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"}},"topics":[{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.9994999766349792,"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"}},{"id":"https://openalex.org/T10085","display_name":"Parkinson's Disease Mechanisms and Treatments","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"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/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":9.999999747378752e-05,"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/amyloid-beta","display_name":"amyloid-beta","score":0.75},{"id":"https://openalex.org/keywords/serotonin-transporter","display_name":"serotonin transporter","score":0.8560000061988831},{"id":"https://openalex.org/keywords/selective-serotonin-reuptake-inhibitors","display_name":"selective serotonin reuptake inhibitors","score":0.9449999928474426},{"id":"https://openalex.org/keywords/fluoxetine","display_name":"fluoxetine","score":0.9760000109672546},{"id":"https://openalex.org/keywords/norfluoxetine","display_name":"norfluoxetine","score":0.9190000295639038},{"id":"https://openalex.org/keywords/alzheimer-s-disease","display_name":"Alzheimer's disease","score":0.6690000295639038},{"id":"https://openalex.org/keywords/caenorhabditis-elegans","display_name":"Caenorhabditis elegans","score":0.8859999775886536},{"id":"https://openalex.org/keywords/depression","display_name":"depression","score":0.4129999876022339},{"id":"https://openalex.org/keywords/off-target-effects","display_name":"off-target effects","score":0.5210000276565552},{"id":"https://openalex.org/keywords/tryptophan-hydroxylase","display_name":"tryptophan hydroxylase","score":0.9020000100135803}],"concepts":[{"id":"https://openalex.org/C2779177272","wikidata":"https://www.wikidata.org/wiki/Q76560","display_name":"Antidepressant","level":3,"score":0.8065670728683472},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6611635684967041},{"id":"https://openalex.org/C2778897192","wikidata":"https://www.wikidata.org/wiki/Q410142","display_name":"Serotonin transporter","level":4,"score":0.6245847344398499},{"id":"https://openalex.org/C2775864247","wikidata":"https://www.wikidata.org/wiki/Q167934","display_name":"Serotonin","level":3,"score":0.602197527885437},{"id":"https://openalex.org/C149011108","wikidata":"https://www.wikidata.org/wiki/Q652985","display_name":"Transporter","level":3,"score":0.5891929268836975},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.5691918730735779},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.5102035999298096},{"id":"https://openalex.org/C2777477808","wikidata":"https://www.wikidata.org/wiki/Q407595","display_name":"Metabolite","level":2,"score":0.4799692630767822},{"id":"https://openalex.org/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.4315780997276306},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.37641000747680664},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.31544923782348633},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.19272670149803162},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.1701328456401825},{"id":"https://openalex.org/C2781161787","wikidata":"https://www.wikidata.org/wiki/Q48360","display_name":"Hippocampus","level":2,"score":0.08065906167030334},{"id":"https://openalex.org/C138885662","wikidata":"https://www.wikidata.org/wiki/Q5891","display_name":"Philosophy","level":0,"score":0.07768100500106812},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.05882728099822998},{"id":"https://openalex.org/C111472728","wikidata":"https://www.wikidata.org/wiki/Q9471","display_name":"Epistemology","level":1,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:harvest.usask.ca:10388/11773","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/10388/11773","pdf_url":"https://harvest.usask.ca/bitstreams/bb11d2be-4b4e-47f2-ae36-59159613e027/download","source":{"id":"https://openalex.org/S7407063267","display_name":"HARVEST (University of Saskatchewan)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},{"id":"mag:2941934997","doi":null,"is_oa":false,"landing_page_url":"https://harvest.usask.ca/handle/10388/11773","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":{"id":"pmh:oai:harvest.usask.ca:10388/11773","doi":null,"is_oa":true,"landing_page_url":"http://hdl.handle.net/10388/11773","pdf_url":"https://harvest.usask.ca/bitstreams/bb11d2be-4b4e-47f2-ae36-59159613e027/download","source":{"id":"https://openalex.org/S7407063267","display_name":"HARVEST (University of Saskatchewan)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":1.0}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320319919","display_name":"Saskatchewan Health Research Foundation","ror":"https://ror.org/00trnds81"},{"id":"https://openalex.org/F4320334593","display_name":"Natural Sciences and Engineering Research Council of Canada","ror":"https://ror.org/01h531d29"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2941934997.pdf","grobid_xml":"https://content.openalex.org/works/W2941934997.grobid-xml"},"referenced_works_count":93,"referenced_works":["https://openalex.org/W1575197904","https://openalex.org/W1932861877","https://openalex.org/W1965879244","https://openalex.org/W1967464880","https://openalex.org/W1973855353","https://openalex.org/W1977925481","https://openalex.org/W1979490511","https://openalex.org/W1980224852","https://openalex.org/W1980314710","https://openalex.org/W1980784555","https://openalex.org/W1981420116","https://openalex.org/W1984009511","https://openalex.org/W1985325561","https://openalex.org/W1986695958","https://openalex.org/W1986777050","https://openalex.org/W1988104043","https://openalex.org/W1990454576","https://openalex.org/W1991536770","https://openalex.org/W1997460720","https://openalex.org/W1998478437","https://openalex.org/W2000954930","https://openalex.org/W2002370647","https://openalex.org/W2003303561","https://openalex.org/W2004649797","https://openalex.org/W2004823323","https://openalex.org/W2005681172","https://openalex.org/W2006615927","https://openalex.org/W2007783013","https://openalex.org/W2018008180","https://openalex.org/W2020713081","https://openalex.org/W2021181758","https://openalex.org/W2022673879","https://openalex.org/W2026970282","https://openalex.org/W2027630696","https://openalex.org/W2030155143","https://openalex.org/W2030182984","https://openalex.org/W2030355018","https://openalex.org/W2031184344","https://openalex.org/W2035872135","https://openalex.org/W2045409916","https://openalex.org/W2045422537","https://openalex.org/W2046209489","https://openalex.org/W2048621255","https://openalex.org/W2048738245","https://openalex.org/W2050591554","https://openalex.org/W2052734595","https://openalex.org/W2052742260","https://openalex.org/W2056421884","https://openalex.org/W2058723245","https://openalex.org/W2058880763","https://openalex.org/W2063808031","https://openalex.org/W2071780847","https://openalex.org/W2073309967","https://openalex.org/W2074005945","https://openalex.org/W2074371966","https://openalex.org/W2076277579","https://openalex.org/W2077844594","https://openalex.org/W2079355643","https://openalex.org/W2082547065","https://openalex.org/W2082599991","https://openalex.org/W2082617364","https://openalex.org/W2084333656","https://openalex.org/W2087281430","https://openalex.org/W2089427043","https://openalex.org/W2092043738","https://openalex.org/W2094590451","https://openalex.org/W2100879756","https://openalex.org/W2101077392","https://openalex.org/W2106931873","https://openalex.org/W2116876598","https://openalex.org/W2117155939","https://openalex.org/W2117513966","https://openalex.org/W2125402398","https://openalex.org/W2126974689","https://openalex.org/W2131830842","https://openalex.org/W2132513137","https://openalex.org/W2133574018","https://openalex.org/W2137944397","https://openalex.org/W2138751812","https://openalex.org/W2142367912","https://openalex.org/W2146254304","https://openalex.org/W2147083367","https://openalex.org/W2150638090","https://openalex.org/W2156606243","https://openalex.org/W2158205505","https://openalex.org/W2168697938","https://openalex.org/W2171682279","https://openalex.org/W2194075469","https://openalex.org/W2325499149","https://openalex.org/W2555740579","https://openalex.org/W2591441084","https://openalex.org/W2599851926","https://openalex.org/W4233829850"],"related_works":["https://openalex.org/W2889330771","https://openalex.org/W2801716790","https://openalex.org/W1977085392","https://openalex.org/W2755615457","https://openalex.org/W3112535304","https://openalex.org/W2949940216","https://openalex.org/W2943280373","https://openalex.org/W1919615929","https://openalex.org/W1974323467","https://openalex.org/W2355755335"],"abstract_inverted_index":{"Depression":[0],"increases":[1],"the":[2,17,25,47,67,77,86,99,109,138,151,167,170,178,204,219,237,243,248,262,274,283,289,328],"risk":[3,12,30,347],"of":[4,10,19,101,112,123,140,153,157,169,185,207,250,255,276,331,340,356,362],"Alzheimer":[5],"disease":[6,79],"(AD);":[7],"however,":[8],"some":[9],"this":[11,211,232,296],"might":[13],"be":[14,94,343],"associated":[15,33],"with":[16,34],"type":[18],"antidepressant":[20],"drug":[21],"used":[22,135],"to":[23,136,177,280,370],"treat":[24],"depression.":[26],"Indeed,":[27],"a":[28,183,201,213,223,258,266,337,351,371],"significant":[29,338],"has":[31,52],"been":[32,53],"selective":[35],"serotonin":[36,43,48,307],"reuptake":[37],"inhibitors":[38],"(SSRIs).":[39],"SSRIs":[40,104,333],"increase":[41],"synaptic":[42],"levels":[44],"by":[45,96,103],"inhibiting":[46,273],"transporter":[49],"(SERT).":[50],"It":[51],"reported":[54],"that":[55,85,217,240,260,281,286],"SERT":[56,102],"can":[57],"transport":[58,358],"molecules":[59],"other":[60],"than":[61],"serotonin.":[62],"One":[63],"such":[64],"molecule":[65],"is":[66,83,165,174],"14":[68],"kDa":[69,89],"protein":[70,73],"\u03b1-synuclein":[71],"(a":[72,121],"which":[74],"accumulates":[75],"in":[76,108,159,194,210,231,247,257,282,295,305,306,373],"Parkinson":[78],"brain).":[80],"Therefore,":[81],"it":[82],"possible":[84],"AD-related,":[87],"4":[88],"beta-amyloid":[90],"(A\u03b2),":[91],"may":[92],"also":[93,229],"transported":[95],"SERT,":[97,208],"and":[98,118,130,145,173,190,323,359],"inhibition":[100,355],"could":[105,342],"inadvertently":[106],"result":[107],"intracellular":[110,360],"accumulation":[111,152,181,361],"A\u03b2":[113,363],"and,":[114],"ultimately,":[115],"cell":[116,132,314],"death":[117],"plaque":[119],"formation":[120],"hallmark":[122],"AD":[124,349],"pathology).":[125],"Caenorhabditis":[126],"elegans":[127,163,196],"(C.":[128],"elegans)":[129],"mammalian":[131,313],"culture":[133],"were":[134,319],"study":[137],"effects":[139],"selected":[141],"SSRIs,":[142],"i.e.":[143],"Fluoxetine":[144,189],"its":[146],"major":[147],"metabolite,":[148],"nor-Fluoxetine,":[149],"on":[150,222,265,302,312,354],"A\u03b2.":[154],"The":[155,253,309],"expression":[156],"A\u03b21-42":[158,220,244,263,290],"our":[160],"transgenic":[161],"C.":[162,195],"strain":[164,235,239,285],"under":[166],"control":[168],"muscle":[171],"promoter":[172],"therefore":[175],"specific":[176],"muscle.":[179],"Any":[180],"causes":[182],"loss":[184],"motility/paralysis":[186],"phenotype.":[187],"Both":[188],"nor-Fluoxetine":[191],"exacerbated":[192,230],"paralysis":[193,256,294],"expressing":[197],"A\u03b21-42.":[198],"To":[199],"confirm":[200],"role":[202],"for":[203,334,348],"worm":[205,214,234,259,297],"analogue":[206],"MOD-5,":[209],"effect,":[212],"was":[215,228,278,299],"generated":[216],"carried":[218,261],"peptide":[221,264],"truncated":[224],"MOD-5":[225],"background.":[226],"Paralysis":[227],"cross-bred":[233],"(versus":[236],"parental":[238,284],"just":[241,287],"expressed":[242,288],"peptide),":[245],"even":[246],"absence":[249],"SSRI":[251],"treatment.":[252],"degree":[254],"TPH-1":[267],"(tryptophan":[268],"hydroxylase)":[269],"null":[270],"background":[271],"(thus,":[272],"synthesis":[275],"serotonin)":[277],"similar":[279],"peptide.":[291],"Thus,":[292],"any":[293,303],"model":[298],"not":[300,320],"dependent":[301],"change":[304,372],"availability.":[308],"experiments":[310],"based":[311,353],"cultures,":[315],"although":[316],"showing":[317],"promise,":[318],"as":[321],"conclusive":[322],"need":[324],"further":[325],"optimization.":[326],"Given":[327],"increased":[329],"practice":[330],"prescribing":[332],"off-label":[335],"purposes,":[336],"number":[339],"individuals":[341],"unknowingly":[344],"put":[345],"at":[346],"through":[350],"mechanism":[352],"SERT-mediated":[357],"peptides.":[364],"These":[365],"observations":[366],"will":[367],"hopefully":[368],"lead":[369],"prescription":[374],"practices.":[375]},"counts_by_year":[],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2019-05-03T00:00:00"}
