Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies
Olfactory dysfunction is one of the prodromal symptoms in dementia with Lewy bodies (DLB). However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derive...
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| Veröffentlicht in: | International journal of molecular sciences 2020-09, Vol.21 (17), p.6371 |
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| creator | Lachén-Montes, Mercedes Mendizuri, Naroa Schvartz, Domitille Fernández-Irigoyen, Joaquín Sánchez, Jean Charles Santamaría, Enrique |
| description | Olfactory dysfunction is one of the prodromal symptoms in dementia with Lewy bodies (DLB). However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derived from DLB subjects compared to neurologically intact controls. A total of 3214 olfactory proteins were quantified, and 99 proteins showed significant alterations in DLB cases. Protein interaction networks disrupted in DLB indicated an imbalance in translation and the synaptic vesicle cycle. These alterations were accompanied by alterations in AKT/MAPK/SEK1/p38 MAPK signaling pathways that showed a distinct expression profile across the OB-olfactory tract (OT) axis. Taken together, our data partially reflect the missing links in the biochemical understanding of olfactory dysfunction in DLB. |
| doi_str_mv | 10.3390/ijms21176371 |
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However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derived from DLB subjects compared to neurologically intact controls. A total of 3214 olfactory proteins were quantified, and 99 proteins showed significant alterations in DLB cases. Protein interaction networks disrupted in DLB indicated an imbalance in translation and the synaptic vesicle cycle. These alterations were accompanied by alterations in AKT/MAPK/SEK1/p38 MAPK signaling pathways that showed a distinct expression profile across the OB-olfactory tract (OT) axis. Taken together, our data partially reflect the missing links in the biochemical understanding of olfactory dysfunction in DLB.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21176371</identifier><identifier>PMID: 32887355</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Aged ; Aged, 80 and over ; AKT protein ; Alzheimer Disease - complications ; Biomarkers - metabolism ; Brain ; Case-Control Studies ; Cognitive ability ; Dementia ; Dementia disorders ; Disease Progression ; Female ; Hallucinations ; Humans ; Kinases ; Lewy bodies ; Lewy Body Disease - complications ; Male ; MAP kinase ; Mass spectrometry ; Metabolism ; Neurodegeneration ; Olfaction ; Olfactory bulb ; Olfactory Nerve Diseases - diagnosis ; Olfactory Nerve Diseases - etiology ; Olfactory Nerve Diseases - metabolism ; Pathology ; Protein synthesis ; Proteins ; Proteome - analysis ; Proteome - metabolism ; Proteomes ; Proteomics ; Scientific imaging ; Smell</subject><ispartof>International journal of molecular sciences, 2020-09, Vol.21 (17), p.6371</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-698eea31ae842ac9f7b4ceb4ee66b544b0a3d410dbc8a8ea7ecdc17483ed1fdb3</citedby><cites>FETCH-LOGICAL-c412t-698eea31ae842ac9f7b4ceb4ee66b544b0a3d410dbc8a8ea7ecdc17483ed1fdb3</cites><orcidid>0000-0001-8046-8102 ; 0000-0003-1133-0462 ; 0000-0001-5072-4099</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503830/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503830/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32887355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lachén-Montes, Mercedes</creatorcontrib><creatorcontrib>Mendizuri, Naroa</creatorcontrib><creatorcontrib>Schvartz, Domitille</creatorcontrib><creatorcontrib>Fernández-Irigoyen, Joaquín</creatorcontrib><creatorcontrib>Sánchez, Jean Charles</creatorcontrib><creatorcontrib>Santamaría, Enrique</creatorcontrib><title>Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Olfactory dysfunction is one of the prodromal symptoms in dementia with Lewy bodies (DLB). However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derived from DLB subjects compared to neurologically intact controls. A total of 3214 olfactory proteins were quantified, and 99 proteins showed significant alterations in DLB cases. Protein interaction networks disrupted in DLB indicated an imbalance in translation and the synaptic vesicle cycle. These alterations were accompanied by alterations in AKT/MAPK/SEK1/p38 MAPK signaling pathways that showed a distinct expression profile across the OB-olfactory tract (OT) axis. Taken together, our data partially reflect the missing links in the biochemical understanding of olfactory dysfunction in DLB.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AKT protein</subject><subject>Alzheimer Disease - complications</subject><subject>Biomarkers - metabolism</subject><subject>Brain</subject><subject>Case-Control Studies</subject><subject>Cognitive ability</subject><subject>Dementia</subject><subject>Dementia disorders</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Hallucinations</subject><subject>Humans</subject><subject>Kinases</subject><subject>Lewy bodies</subject><subject>Lewy Body Disease - complications</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Mass spectrometry</subject><subject>Metabolism</subject><subject>Neurodegeneration</subject><subject>Olfaction</subject><subject>Olfactory bulb</subject><subject>Olfactory Nerve Diseases - diagnosis</subject><subject>Olfactory Nerve Diseases - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lachén-Montes, Mercedes</au><au>Mendizuri, Naroa</au><au>Schvartz, Domitille</au><au>Fernández-Irigoyen, Joaquín</au><au>Sánchez, Jean Charles</au><au>Santamaría, Enrique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-09-02</date><risdate>2020</risdate><volume>21</volume><issue>17</issue><spage>6371</spage><pages>6371-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Olfactory dysfunction is one of the prodromal symptoms in dementia with Lewy bodies (DLB). However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derived from DLB subjects compared to neurologically intact controls. A total of 3214 olfactory proteins were quantified, and 99 proteins showed significant alterations in DLB cases. Protein interaction networks disrupted in DLB indicated an imbalance in translation and the synaptic vesicle cycle. These alterations were accompanied by alterations in AKT/MAPK/SEK1/p38 MAPK signaling pathways that showed a distinct expression profile across the OB-olfactory tract (OT) axis. 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| subjects | Aged Aged, 80 and over AKT protein Alzheimer Disease - complications Biomarkers - metabolism Brain Case-Control Studies Cognitive ability Dementia Dementia disorders Disease Progression Female Hallucinations Humans Kinases Lewy bodies Lewy Body Disease - complications Male MAP kinase Mass spectrometry Metabolism Neurodegeneration Olfaction Olfactory bulb Olfactory Nerve Diseases - diagnosis Olfactory Nerve Diseases - etiology Olfactory Nerve Diseases - metabolism Pathology Protein synthesis Proteins Proteome - analysis Proteome - metabolism Proteomes Proteomics Scientific imaging Smell |
| title | Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies |
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