{"id":"https://openalex.org/W7204856799","doi":"https://doi.org/10.3390/biom16101470","title":"Serotonergic Dysfunction and the Interacting Role of TAR DNA-Binding Protein 43 in the Progression of Amyotrophic Lateral Sclerosis: A Scoping Review","display_name":"Serotonergic Dysfunction and the Interacting Role of TAR DNA-Binding Protein 43 in the Progression of Amyotrophic Lateral Sclerosis: A Scoping Review","publication_year":2026,"publication_date":"2026-10-09","ids":{"openalex":"https://openalex.org/W7204856799","doi":"https://doi.org/10.3390/biom16101470","pmid":"https://pubmed.ncbi.nlm.nih.gov/42939724","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13702111"},"language":"en","primary_location":{"id":"doi:10.3390/biom16101470","doi":"https://doi.org/10.3390/biom16101470","is_oa":true,"landing_page_url":"https://doi.org/10.3390/biom16101470","pdf_url":null,"source":{"id":"https://openalex.org/S4210236520","display_name":"Biomolecules","issn_l":"2218-273X","issn":["2218-273X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","medline","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biomolecules","raw_type":"journal-article"},"volume":null,"type":"review","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3390/biom16101470","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5149879588","display_name":"Lauren Hutchison","orcid":"https://orcid.org/0009-0001-5405-1044","observed_orcids":["https://orcid.org/0009-0001-5405-1044"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lauren L. Hutchison","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0009-0001-5405-1044","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5148804642","display_name":"Makenna M. Parkes","orcid":"https://orcid.org/0009-0007-4605-2470","observed_orcids":["https://orcid.org/0009-0007-4605-2470"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Makenna M. Parkes","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0009-0007-4605-2470","affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5067234869","display_name":"Erik P. Pioro","orcid":"https://orcid.org/0000-0002-0737-6065","observed_orcids":["https://orcid.org/0000-0002-0737-6065"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Erik P. Pioro","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-0737-6065","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5067234869"],"corresponding_institution_ids":[],"apc_list":{"value":2700,"currency":"CHF","value_usd":3258},"apc_paid":{"value":2700,"currency":"CHF","value_usd":3258},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.45236275,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"16","issue":"10","first_page":"1470","last_page":"1470"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10855","display_name":"Amyotrophic Lateral Sclerosis Research","score":1.0,"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"}},"topics":[{"id":"https://openalex.org/T10855","display_name":"Amyotrophic Lateral Sclerosis Research","score":1.0,"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/T10086","display_name":"Alzheimer's disease research and treatments","score":0.0,"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/T10441","display_name":"Muscle Physiology and Disorders","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular 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"}}],"keywords":[{"id":"https://openalex.org/keywords/amyotrophic-lateral-sclerosis","display_name":"amyotrophic lateral sclerosis","score":1.0},{"id":"https://openalex.org/keywords/serotonergic-dysfunction","display_name":"serotonergic dysfunction","score":0.9179999828338623},{"id":"https://openalex.org/keywords/serotonin","display_name":"serotonin","score":0.7350000143051147},{"id":"https://openalex.org/keywords/tdp-43-proteinopathy","display_name":"TDP-43 proteinopathy","score":0.921999990940094},{"id":"https://openalex.org/keywords/tdp-43-aggregation","display_name":"TDP-43 aggregation","score":0.890999972820282},{"id":"https://openalex.org/keywords/serotonergic-neurotransmission","display_name":"serotonergic neurotransmission","score":0.6320000290870667},{"id":"https://openalex.org/keywords/excitotoxicity","display_name":"excitotoxicity","score":0.8399999737739563},{"id":"https://openalex.org/keywords/network-hyperexcitability","display_name":"network hyperexcitability","score":0.9319999814033508},{"id":"https://openalex.org/keywords/disease-progression","display_name":"disease progression","score":0.675000011920929},{"id":"https://openalex.org/keywords/motor-neuron-degeneration","display_name":"motor neuron degeneration","score":0.5989999771118164}],"concepts":[{"id":"https://openalex.org/C37000724","wikidata":"https://www.wikidata.org/wiki/Q50430226","display_name":"Serotonergic","level":4,"score":0.9635999798774719},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.7258999943733215},{"id":"https://openalex.org/C2780596555","wikidata":"https://www.wikidata.org/wiki/Q206901","display_name":"Amyotrophic lateral sclerosis","level":3,"score":0.6431000232696533},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.5889000296592712},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4316999912261963},{"id":"https://openalex.org/C2777865548","wikidata":"https://www.wikidata.org/wiki/Q2061493","display_name":"Raphe nuclei","level":5,"score":0.3944999873638153},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.39419999718666077},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.37439998984336853},{"id":"https://openalex.org/C2775864247","wikidata":"https://www.wikidata.org/wiki/Q167934","display_name":"Serotonin","level":3,"score":0.36880001425743103},{"id":"https://openalex.org/C15744967","wikidata":"https://www.wikidata.org/wiki/Q9418","display_name":"Psychology","level":0,"score":0.3418999910354614},{"id":"https://openalex.org/C200170125","wikidata":"https://www.wikidata.org/wiki/Q969316","display_name":"Neurotransmission","level":3,"score":0.31540000438690186},{"id":"https://openalex.org/C2777440831","wikidata":"https://www.wikidata.org/wiki/Q2376264","display_name":"Synucleinopathies","level":5,"score":0.2757999897003174},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.27459999918937683},{"id":"https://openalex.org/C87753298","wikidata":"https://www.wikidata.org/wiki/Q17157137","display_name":"Neuroinflammation","level":3,"score":0.2655999958515167}],"mesh":[{"descriptor_ui":"D000690","descriptor_name":"Amyotrophic Lateral Sclerosis","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D000690","descriptor_name":"Amyotrophic Lateral Sclerosis","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D000690","descriptor_name":"Amyotrophic Lateral Sclerosis","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004268","descriptor_name":"DNA-Binding Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012701","descriptor_name":"Serotonin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D018450","descriptor_name":"Disease Progression","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":5,"locations":[{"id":"doi:10.3390/biom16101470","doi":"https://doi.org/10.3390/biom16101470","is_oa":true,"landing_page_url":"https://doi.org/10.3390/biom16101470","pdf_url":null,"source":{"id":"https://openalex.org/S4210236520","display_name":"Biomolecules","issn_l":"2218-273X","issn":["2218-273X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","medline","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biomolecules","raw_type":"journal-article"},{"id":"doi:10.20944/preprints202608.2190.v1","doi":"https://doi.org/10.20944/preprints202608.2190.v1","is_oa":true,"landing_page_url":"https://doi.org/10.20944/preprints202608.2190.v1","pdf_url":null,"source":{"id":"https://openalex.org/S6309402219","display_name":"Preprints.org","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},{"id":"pmh:oai:pubmedcentral.nih.gov:13702111","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13702111/","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13702111/pdf/biomolecules-16-01470.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":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biomolecules","raw_type":"Text"},{"id":"pmid:42939724","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42939724","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":"Biomolecules","raw_type":"Journal Article"},{"id":"pmh:oai:doaj.org/article:88e1863b1da34900a5a0f2eb4ef791b4","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/88e1863b1da34900a5a0f2eb4ef791b4","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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Biomolecules, Vol 16, Iss 10, p 1470 (2026)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3390/biom16101470","doi":"https://doi.org/10.3390/biom16101470","is_oa":true,"landing_page_url":"https://doi.org/10.3390/biom16101470","pdf_url":null,"source":{"id":"https://openalex.org/S4210236520","display_name":"Biomolecules","issn_l":"2218-273X","issn":["2218-273X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","medline","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biomolecules","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9922999739646912,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[{"id":"https://openalex.org/study-designs/systematic-review","display_name":"Systematic Review"}],"awards":[],"funders":[{"id":"https://openalex.org/F4320313332","display_name":"Faculty of Medicine, University of British Columbia","ror":null}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7204856799.pdf","grobid_xml":"https://content.openalex.org/works/W7204856799.grobid-xml"},"referenced_works_count":31,"referenced_works":["https://openalex.org/W1974608614","https://openalex.org/W1978306592","https://openalex.org/W1999030539","https://openalex.org/W2024747286","https://openalex.org/W2025336623","https://openalex.org/W2028611597","https://openalex.org/W2036906482","https://openalex.org/W2049906849","https://openalex.org/W2050626075","https://openalex.org/W2052332287","https://openalex.org/W2135190897","https://openalex.org/W2223403503","https://openalex.org/W2309136250","https://openalex.org/W2753430298","https://openalex.org/W2769269450","https://openalex.org/W2789293490","https://openalex.org/W2794236229","https://openalex.org/W2891378911","https://openalex.org/W2911237161","https://openalex.org/W3023397682","https://openalex.org/W3049104711","https://openalex.org/W3118615836","https://openalex.org/W3171552186","https://openalex.org/W4317107445","https://openalex.org/W4318927808","https://openalex.org/W4391304213","https://openalex.org/W4396854324","https://openalex.org/W4396906626","https://openalex.org/W4412595237","https://openalex.org/W4414127436","https://openalex.org/W7125526560"],"related_works":["https://openalex.org/W3094532985","https://openalex.org/W3140660898","https://openalex.org/W2033937032","https://openalex.org/W4318927808","https://openalex.org/W7127158661","https://openalex.org/W7128747128","https://openalex.org/W4409202192","https://openalex.org/W6939658981","https://openalex.org/W2123051708","https://openalex.org/W4313250838"],"abstract_inverted_index":{"Amyotrophic":[0],"lateral":[1],"sclerosis":[2],"(ALS)":[3],"is":[4,155,215],"a":[5,156,216],"progressive":[6],"neurodegenerative":[7],"disease":[8,40,203],"characterized":[9,162],"by":[10,117,140,163,194,235],"the":[11,253],"loss":[12],"of":[13,21,53,145,159,168,218],"mo-tor":[14],"neurons":[15],"and":[16,25,67,86,104,113,148,166,183,197,209,229,258],"widespread":[17],"neural":[18],"dysfunction.":[19],"Loss":[20],"serotonin":[22,184],"(5-HT)":[23],"signaling":[24],"TAR":[26],"DNA-binding":[27],"protein":[28],"43":[29],"(TDP-43)":[30],"dysfunction":[31,66,131,199,228],"have":[32,172],"both":[33,195],"been":[34,245],"identified":[35,134,173],"as":[36],"contributing":[37],"factors":[38],"to":[39,47,57,107,251],"progression,":[41,161],"although":[42],"their":[43],"rela-tionship":[44],"has":[45,243],"yet":[46],"be":[48,133,233],"fully":[49],"defined.":[50],"The":[51],"objective":[52],"this":[54],"review":[55,74],"was":[56,75],"assess":[58],"whether":[59],"any":[60],"mechanistic":[61],"links":[62,175],"exist":[63],"between":[64,176,224,255],"serotonergic":[65,130,181,196],"TDP-43":[68,105,153,179,189,198,230],"proteinopathy":[69,154,231],"in":[70,77,136,150,238],"ALS.":[71],"A":[72],"scoping":[73],"conducted":[76],"accordance":[78],"with":[79,202],"Preferred":[80],"Reporting":[81],"Items":[82],"for":[83,89,97],"Systematic":[84],"Reviews":[85,91],"Meta-Analyses":[87],"extension":[88],"Scoping":[90],"(PRISMA-ScR)":[92],"guidelines.":[93],"Databases":[94],"were":[95,111,121],"queried":[96],"peer-reviewed":[98],"literature":[99,127],"concerning":[100],"ALS":[101,137,160],"pathophysiology,":[102],"5-HT,":[103],"(1946":[106],"January":[108],"2026).":[109],"Articles":[110],"screened":[112],"data":[114],"independently":[115],"extracted":[116],"two":[118],"reviewers,":[119],"which":[120],"subsequently":[122],"synthesized":[123],"qualitatively":[124],"(n=14).":[125],"Current":[126],"suggests":[128],"that":[129],"can":[132],"early":[135],"pathology,":[138],"indicated":[139],"decreased":[141],"5-HT":[142],"concentration,":[143],"degeneration":[144],"raphe":[146],"projections,":[147],"changes":[149],"receptor":[151],"activity.":[152],"defining":[157],"characteristic":[158],"cytoplasmic":[164],"mislocalization":[165],"aggregation":[167],"TDP-43.":[169],"Additionally,":[170],"studies":[171],"bidirectional":[174],"these":[177,225,256],"dysfunctions:":[178],"impairs":[180],"transmission":[182],"deficiency":[185],"may":[186,232],"drive":[187],"patholog-ical":[188],"aggregation.":[190],"Many":[191],"mechanisms":[192,237],"affected":[193],"are":[200],"associated":[201],"progression":[204],"including":[205],"excitotoxicity,":[206],"metabolic":[207],"disturbances,":[208],"network":[210],"hyperexcitability.":[211],"Despite":[212],"this,":[213],"there":[214],"lack":[217],"direct":[219],"experimental":[220],"evidence":[221],"elucidating":[222],"connections":[223],"pathologies.":[226],"Serotonergic":[227],"linked":[234],"shared":[236],"ALS,":[239],"though":[240],"specific":[241],"causality":[242],"not":[244],"identified.":[246],"Further":[247],"research":[248],"should":[249],"aim":[250],"clarify":[252],"connection":[254],"processes":[257],"discover":[259],"therapeutic":[260],"targets.":[261]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-09-01T00:00:00"}