{"doi":"10.1159/000295662","title":"Retinoids as a Perspective in Treatment of Alzheimer’s Disease","abstract":"<jats:p>&lt;i&gt;Background:&lt;/i&gt; In the past, we demonstrated that the disintegrin metalloproteinase ADAM10 has α-secretase activity in vitro and in cultured cells. We also found out that moderate overexpression of this proteinase inhibits Aβ peptide production and prevents the formation of amyloid plaques in an Alzheimer’s disease (AD) mouse model. Moreover, it corrects early hippocampal defects like LTP impairment and increases cortical synaptogenesis. &lt;i&gt;Objective:&lt;/i&gt; Upregulation of ADAM10 might be an alternative approach concerning AD therapy. Our current research therefore focuses on substances and/or pathways which regulate ADAM10 gene expression. &lt;i&gt;Methods:&lt;/i&gt; Analyses of ADAM10 promoter activity were performed in human and murine neuroblastoma cell lines and important findings were validated in an AD mouse model. &lt;i&gt;Results:&lt;/i&gt; The outcome of our investigations indicates that a heterodimeric retinoid receptor mediates the activation of the ADAM10 promoter by all-&lt;i&gt;trans&lt;/i&gt;-retinoic acid. This then results in enhanced ADAM10 expression, pronounced APPs-α secretion and diminished proteolytic processing products of the amyloidogenic pathway (APPs-β, Aβ). &lt;i&gt;Conclusion:&lt;/i&gt; Nontoxic synthetic retinoids – like acitretin – offer a valuable therapeutic approach in treatment of AD by moderately enhancing ADAM10 gene expression.</jats:p>","journal":"Neurodegenerative Diseases","year":2010,"id":589058,"datarank":0.9522647015315868,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.5029048604984881,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.5029048604984881,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":15,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1507069,"name":"Frank Tippmann","orcid":null,"position":1,"is_corresponding":false},{"id":798103,"name":"Kristina Endres","orcid":"0000-0002-1099-8287","position":2,"is_corresponding":false},{"id":1507068,"name":"Falk Fahrenholz","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Retinoids as a Perspective in Treatment of Alzheimer’s Disease","abstract":"<jats:p>&lt;i&gt;Background:&lt;/i&gt; In the past, we demonstrated that the disintegrin metalloproteinase ADAM10 has α-secretase activity in vitro and in cultured cells. We also found out that moderate overexpression of this proteinase inhibits Aβ peptide production and prevents the formation of amyloid plaques in an Alzheimer’s disease (AD) mouse model. Moreover, it corrects early hippocampal defects like LTP impairment and increases cortical synaptogenesis. &lt;i&gt;Objective:&lt;/i&gt; Upregulation of ADAM10 might be an alternative approach concerning AD therapy. Our current research therefore focuses on substances and/or pathways which regulate ADAM10 gene expression. &lt;i&gt;Methods:&lt;/i&gt; Analyses of ADAM10 promoter activity were performed in human and murine neuroblastoma cell lines and important findings were validated in an AD mouse model. &lt;i&gt;Results:&lt;/i&gt; The outcome of our investigations indicates that a heterodimeric retinoid receptor mediates the activation of the ADAM10 promoter by all-&lt;i&gt;trans&lt;/i&gt;-retinoic acid. This then results in enhanced ADAM10 expression, pronounced APPs-α secretion and diminished proteolytic processing products of the amyloidogenic pathway (APPs-β, Aβ). &lt;i&gt;Conclusion:&lt;/i&gt; Nontoxic synthetic retinoids – like acitretin – offer a valuable therapeutic approach in treatment of AD by moderately enhancing ADAM10 gene expression.</jats:p>","is_dataset_classified":null,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20224284","pmcid":null,"openalex_id":"https://openalex.org/W1966319981","authors":[],"funders":[],"total_grants":0,"fwci":1.7209,"citation_percentile":0.82779982,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":3},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2019,"count":2},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2025,"count":1}],"oa_status":"closed","license":"https://www.karger.com/Services/SiteLicenses","oa_locations":[{"url":"https://www.karger.com/Article/Pdf/295662","host_type":"publisher"},{"url":"https://doi.org/10.1159/000295662","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20224284","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Retinoids in leukemia and cellular processes","Protease and Inhibitor Mechanisms","Medicine","Biology","ADAM Proteins","ADAM10 Protein","Amyloid Precursor Protein Secretases","Animals","Cell Line, Tumor","Chromones","Dose-Response Relationship, Drug","Enzyme Inhibitors","Humans","Membrane Proteins","Mice","Morpholines","Neuroblastoma","Retinoids","Signal Transduction","Terpenes","Up-Regulation","Vitamins"],"mesh_terms":["ADAM10 Protein","Animals","Chromones","Dose-Response Relationship, Drug","Enzyme Inhibitors","Humans","Membrane Proteins","Morpholines","Neuroblastoma","Retinoids","Terpenes","Vitamins","Signal Transduction","Up-Regulation","Cell Line, Tumor","Mice","ADAM Proteins","Amyloid Precursor Protein Secretases"],"keywords":["ADAM10","Downregulation and upregulation","Alpha secretase","Retinoid","Disintegrin","Retinoic acid","Metalloproteinase","Cancer research","Biology","Alzheimer's disease","Amyloid precursor protein","Cell biology","Chemistry","Molecular biology","Cell culture","Internal medicine","Medicine","Gene","Biochemistry","Disease","Matrix metalloproteinase","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-23T12:24:02.506030Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}