{"id":"https://openalex.org/W4399157083","doi":"https://doi.org/10.3389/fnagi.2024.1394807","title":"Cathepsin-mediated regulation of alpha-synuclein in Parkinson\u2019s disease: a Mendelian randomization study","display_name":"Cathepsin-mediated regulation of alpha-synuclein in Parkinson\u2019s disease: a Mendelian randomization study","publication_year":2024,"publication_date":"2024-05-30","ids":{"openalex":"https://openalex.org/W4399157083","doi":"https://doi.org/10.3389/fnagi.2024.1394807","pmid":"https://pubmed.ncbi.nlm.nih.gov/38872630"},"language":"en","primary_location":{"id":"doi:10.3389/fnagi.2024.1394807","doi":"https://doi.org/10.3389/fnagi.2024.1394807","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fnagi.2024.1394807","pdf_url":null,"source":{"id":"https://openalex.org/S118428158","display_name":"Frontiers in Aging Neuroscience","issn_l":"1663-4365","issn":["1663-4365"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","jufo-1","ki-jl-1","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Aging Neuroscience","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3389/fnagi.2024.1394807","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5029386363","display_name":"Liyu Lin","orcid":"https://orcid.org/0009-0008-9111-3591","observed_orcids":["https://orcid.org/0009-0008-9111-3591","https://orcid.org/0009-0008-0307-348X"]},"institutions":[{"id":"https://openalex.org/I117532281","display_name":"Guangzhou University of Chinese Medicine","ror":"https://ror.org/03qb7bg95","country_code":"CN","type":"education","lineage":["https://openalex.org/I117532281"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Liyu Lin","raw_affiliation_strings":["The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China","institution_ids":["https://openalex.org/I117532281"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5114170200","display_name":"Zilun Wu","orcid":"https://orcid.org/0009-0000-1136-2822","observed_orcids":["https://orcid.org/0009-0000-1136-2822"]},"institutions":[{"id":"https://openalex.org/I117532281","display_name":"Guangzhou University of Chinese Medicine","ror":"https://ror.org/03qb7bg95","country_code":"CN","type":"education","lineage":["https://openalex.org/I117532281"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zilun Wu","raw_affiliation_strings":["The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China","institution_ids":["https://openalex.org/I117532281"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100594606","display_name":"Haocheng Luo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I117532281","display_name":"Guangzhou University of Chinese Medicine","ror":"https://ror.org/03qb7bg95","country_code":"CN","type":"education","lineage":["https://openalex.org/I117532281"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Haocheng Luo","raw_affiliation_strings":["The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China","institution_ids":["https://openalex.org/I117532281"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5089413090","display_name":"Yunxuan Huang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210105832","display_name":"First Affiliated Hospital of Guangzhou University of Chinese Medicine","ror":"https://ror.org/01mxpdw03","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210105832"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Yunxuan Huang","raw_affiliation_strings":["The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China","institution_ids":["https://openalex.org/I4210105832"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5089413090"],"corresponding_institution_ids":["https://openalex.org/I4210105832"],"apc_list":{"value":3295,"currency":"USD","value_usd":3295},"apc_paid":{"value":3295,"currency":"USD","value_usd":3295},"fwci":2.329,"has_fulltext":true,"cited_by_count":10,"citation_normalized_percentile":{"value":0.8873822,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"16","issue":null,"first_page":"1394807","last_page":"1394807"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10085","display_name":"Parkinson's Disease Mechanisms and Treatments","score":0.9945999979972839,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Neurology"},"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/T10085","display_name":"Parkinson's Disease Mechanisms and Treatments","score":0.9945999979972839,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"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/T10261","display_name":"Genetic Associations and Epidemiology","score":0.003700000001117587,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T13991","display_name":"Nuclear Receptors and Signaling","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/parkinson-s-disease","display_name":"Parkinson's disease","score":0.9760000109672546},{"id":"https://openalex.org/keywords/cathepsins","display_name":"cathepsins","score":0.9879999756813049},{"id":"https://openalex.org/keywords/alpha-synuclein","display_name":"alpha-synuclein","score":0.9539999961853027},{"id":"https://openalex.org/keywords/cathepsin-b","display_name":"cathepsin B","score":0.9559999704360962},{"id":"https://openalex.org/keywords/cathepsin-h","display_name":"cathepsin H","score":0.9620000123977661},{"id":"https://openalex.org/keywords/cathepsin-s","display_name":"cathepsin S","score":1.0},{"id":"https://openalex.org/keywords/cathepsin-d","display_name":"cathepsin D","score":0.6489999890327454},{"id":"https://openalex.org/keywords/cathepsin-e","display_name":"cathepsin E","score":0.7580000162124634},{"id":"https://openalex.org/keywords/cathepsin-f","display_name":"cathepsin F","score":0.8240000009536743},{"id":"https://openalex.org/keywords/cathepsin-g","display_name":"cathepsin G","score":0.7990000247955322},{"id":"https://openalex.org/keywords/cathepsin-l","display_name":"cathepsin L","score":0.7559999823570251},{"id":"https://openalex.org/keywords/proteasome","display_name":"proteasome","score":0.42899999022483826},{"id":"https://openalex.org/keywords/proteolysis","display_name":"proteolysis","score":0.4350000023841858},{"id":"https://openalex.org/keywords/causal-relationship","display_name":"causal relationship","score":0.3409999907016754},{"id":"https://openalex.org/keywords/expression-quantitative-trait-loci","display_name":"expression quantitative trait loci","score":0.7860000133514404}],"concepts":[{"id":"https://openalex.org/C2779901538","wikidata":"https://www.wikidata.org/wiki/Q6816584","display_name":"Mendelian randomization","level":5,"score":0.7634212374687195},{"id":"https://openalex.org/C167844969","wikidata":"https://www.wikidata.org/wiki/Q426245","display_name":"Cathepsin","level":3,"score":0.5016787052154541},{"id":"https://openalex.org/C95190672","wikidata":"https://www.wikidata.org/wiki/Q815382","display_name":"Meta-analysis","level":2,"score":0.44959795475006104},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4278789758682251},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3327367305755615},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.31608593463897705},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2987824082374573},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.1817193627357483},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.08829212188720703},{"id":"https://openalex.org/C135763542","wikidata":"https://www.wikidata.org/wiki/Q106016","display_name":"Genotype","level":3,"score":0.07130292057991028},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.0},{"id":"https://openalex.org/C2993967602","wikidata":"https://www.wikidata.org/wiki/Q5532932","display_name":"Genetic variants","level":4,"score":0.0}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.3389/fnagi.2024.1394807","doi":"https://doi.org/10.3389/fnagi.2024.1394807","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fnagi.2024.1394807","pdf_url":null,"source":{"id":"https://openalex.org/S118428158","display_name":"Frontiers in Aging Neuroscience","issn_l":"1663-4365","issn":["1663-4365"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","jufo-1","ki-jl-1","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Aging Neuroscience","raw_type":"journal-article"},{"id":"pmid:38872630","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/38872630","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in aging neuroscience","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:11170285","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11170285","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11170285/pdf/fnagi-16-1394807.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Front Aging Neurosci","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:4a85cc9cae25482cb73f9143f40cab80","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/4a85cc9cae25482cb73f9143f40cab80","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","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":"Frontiers in Aging Neuroscience, Vol 16 (2024)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fnagi.2024.1394807","doi":"https://doi.org/10.3389/fnagi.2024.1394807","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fnagi.2024.1394807","pdf_url":null,"source":{"id":"https://openalex.org/S118428158","display_name":"Frontiers in Aging Neuroscience","issn_l":"1663-4365","issn":["1663-4365"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","jufo-1","ki-jl-1","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Aging Neuroscience","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9922999739646912,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","score":0.800000011920929,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Observational Study","id":"https://openalex.org/study-designs/observational-study"}],"awards":[],"funders":[{"id":"https://openalex.org/F4320334626","display_name":"Medical Research Council","ror":"https://ror.org/03x94j517"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":38,"referenced_works":["https://openalex.org/W1905058580","https://openalex.org/W1907174433","https://openalex.org/W1975139823","https://openalex.org/W2015019618","https://openalex.org/W2017287105","https://openalex.org/W2068785219","https://openalex.org/W2106036991","https://openalex.org/W2112203259","https://openalex.org/W2113699335","https://openalex.org/W2115478133","https://openalex.org/W2168432448","https://openalex.org/W2265865881","https://openalex.org/W2275325314","https://openalex.org/W2324862792","https://openalex.org/W2346760531","https://openalex.org/W2472421578","https://openalex.org/W2522256697","https://openalex.org/W2614566443","https://openalex.org/W2763924102","https://openalex.org/W2791144662","https://openalex.org/W2805712258","https://openalex.org/W2810852503","https://openalex.org/W2818417770","https://openalex.org/W2886059981","https://openalex.org/W2905086723","https://openalex.org/W2913044717","https://openalex.org/W2916913984","https://openalex.org/W2945443042","https://openalex.org/W2984058577","https://openalex.org/W2993040769","https://openalex.org/W4200462975","https://openalex.org/W4206481149","https://openalex.org/W4211103501","https://openalex.org/W4220817598","https://openalex.org/W4283528698","https://openalex.org/W4309553272","https://openalex.org/W4387432576","https://openalex.org/W4404664480"],"related_works":["https://openalex.org/W4391375266","https://openalex.org/W2901309888","https://openalex.org/W2169283889","https://openalex.org/W4210703904","https://openalex.org/W2082860237","https://openalex.org/W2052821216","https://openalex.org/W1136751063","https://openalex.org/W3111647380","https://openalex.org/W2036527494","https://openalex.org/W2119695867"],"abstract_inverted_index":{"Objective":[0],"The":[1,70,102],"observational":[2],"association":[3,322],"between":[4,34,65,298,323],"cathepsin":[5,35,197,215,228],"and":[6,36,43,56,68,96,139,171,226,300,308,328,344,365,373],"Parkinson\u2019s":[7],"disease":[8,371],"(PD)":[9],"has":[10],"been":[11],"partially":[12],"explored":[13],"in":[14,262],"previous":[15],"research.":[16],"However,":[17],"the":[18,31,45,62,78,99,108,136,145,267,270,280,334,360],"causal":[19,32,63],"relationship":[20,64],"remains":[21],"unclear.":[22],"In":[23,266,312],"this":[24,314],"study,":[25],"our":[26,273],"objective":[27],"is":[28,302],"to":[29,73,89,143,186],"investigate":[30],"link":[33],"PD":[37,90,119,189,203,242,301,330,364],"using":[38,118],"Mendelian":[39],"randomization":[40],"(MR)":[41],"analysis":[42,115,132,170,173],"elucidate":[44],"underlying":[46,271],"mechanisms":[47,153,362],"governing":[48],"their":[49],"interaction.":[50],"Methods":[51],"Utilizing":[52],"bidirectional":[53,263],"two-sample":[54],"MR":[55,114,160,169,193,249,264,307,315],"multivariable":[57],"MR,":[58],"we":[59],"systematically":[60],"investigates":[61],"nine":[66],"cathepsins":[67,74],"PD.":[69,353],"data":[71,87,120,182],"pertaining":[72],"were":[75,91,141,162,174,251,260],"obtained":[76],"from":[77,93,121,147],"Integrative":[79],"Epidemiology":[80],"Unit":[81],"(IEU)":[82],"Open":[83],"GWAS":[84],"Project,":[85],"while":[86,213],"related":[88,185],"sourced":[92],"versions":[94],"R9":[95],"R10":[97,137],"of":[98,127,183,269,282,326,336,342,352,363],"FinnGen":[100],"database.":[101],"primary":[103],"analytical":[104],"method":[105],"utilized":[106],"was":[107,133],"inverse":[109],"variance":[110],"weighted":[111],"(IVW),":[112],"with":[113,167,188,201,240,253,348],"initially":[116],"conducted":[117,175],"R9,":[122],"complemented":[123],"by":[124,154,304,333],"a":[125,293],"series":[126],"sensitivity":[128],"analyses.":[129],"Subsequently,":[130],"replication":[131],"performed":[134,163],"on":[135,164,176],"dataset,":[138],"meta-analysis":[140],"employed":[142],"merge":[144],"findings":[146,274,355],"both":[148,305],"datasets.":[149],"To":[150],"explore":[151],"potential":[152,367],"which":[155],"Cathepsins":[156,166],"may":[157],"impact":[158],"PD,":[159],"analyses":[161,194],"significant":[165,258],"alpha-synuclein.":[168],"colocalization":[172,309],"expression":[177],"quantitative":[178],"trait":[179],"loci":[180],"(eQTL)":[181],"gene":[184],"alpha-synuclein":[187,283,299,337],"data.":[190],"Result":[191],"Forward":[192],"revealed":[195],"more":[196,214,227],"B":[198],"(CTSB)":[199],"associated":[200,239,347],"less":[202],"risk":[204,351],"(OR":[205,218,231,284],"=":[206,211,219,224,232,237,285,290],"0.898,":[207],"95%CI:":[208,221,234,287],"0.834\u20130.966,":[209],"p":[210,223,236,289],"0.004),":[212],"H":[216],"(CTSH)":[217],"1.076,":[220,233],"1.007\u20131.149,":[222],"0.029)":[225],"S":[229],"(CTSS)":[230],"1.007\u20131.150,":[235],"0.030)":[238],"increasing":[241],"risk.":[243],"Meta-analyses":[244],"validated":[245],"these":[246],"associations.":[247],"Multivariate":[248],"Results":[250],"consistent":[252],"those":[254],"before":[255],"adjustment.":[256],"No":[257],"results":[259],"observed":[261],"analysis.":[265,310],"investigation":[268],"mechanism,":[272],"demonstrate":[275],"that":[276],"CTSB":[277,327],"significantly":[278],"reduces":[279],"levels":[281,325,341],"0.909,":[286],"0.841\u20130.983,":[288],"0.017).":[291],"Concurrently,":[292],"genetically":[294],"determined":[295],"positive":[296],"correlation":[297],"illuminated":[303],"eQTL":[306],"Conclusion":[311],"conclusion,":[313],"study":[316],"yields":[317],"robust":[318],"evidence":[319],"suggesting":[320],"an":[321,349],"elevated":[324],"reduced":[329],"risk,":[331],"mediated":[332],"downregulation":[335],"levels.":[338],"Conversely,":[339],"higher":[340],"CTSH":[343],"CTSS":[345],"are":[346],"increased":[350],"These":[354],"offer":[356],"novel":[357],"insights":[358],"into":[359],"pathophysiological":[361],"identify":[366],"drug":[368],"targets":[369],"for":[370],"prevention":[372],"treatment":[374],"warranting":[375],"further":[376],"clinical":[377],"investigations.":[378]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":7},{"year":2024,"cited_by_count":1}],"updated_date":"2026-10-08T09:06:37.294493","created_date":"2025-10-10T00:00:00"}