Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease
| Main Author: | |
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| Publication Date: | 2024 |
| Other Authors: | , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | http://hdl.handle.net/10362/166668 |
Summary: | Publisher Copyright: © 2024, The Author(s). |
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Altered expression of Sialyl Lewis X in experimental models of Parkinson’s diseaseGlycosylationMPTPParkinson’s diseaseSialyl Lewis XMolecular MedicineDrug DiscoveryGenetics(clinical)Publisher Copyright: © 2024, The Author(s).Abstract: The mechanisms underlying neurodegeneration in Parkinson’s disease (PD) are still not fully understood. Glycosylation is an important post-translational modification that affects protein function, cell-cell contacts and inflammation and can be modified in pathologic conditions. Although the involvement of aberrant glycosylation has been proposed for PD, the knowledge of the diversity of glycans and their role in PD is still minimal. Sialyl Lewis X (sLeX) is a sialylated and fucosylated tetrasaccharide with essential roles in cell-to-cell recognition processes. Pathological conditions and pro-inflammatory mediators can up-regulate sLeX expression on cell surfaces, which has important consequences in intracellular signalling and immune function. Here, we investigated the expression of this glycan using in vivo and in vitro models of PD. We show the activation of deleterious glycation-related pathways in mouse striatum upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin-based model of PD. Importantly, our results show that MPTP triggers the presentation of more proteins decorated with sLeX in mouse cortex and striatum in a time-dependent manner, as well as increased mRNA expression of its rate-limiting enzyme fucosyltransferase 7. sLeX is expressed in neurons, including dopaminergic neurons, and microglia. Although the underlying mechanism that drives increased sLeX epitopes, the nature of the protein scaffolds and their functional importance in PD remain unknown, our data suggest for the first time that sLeX in the brain may have a role in neuronal signalling and immunomodulation in pathological conditions. Key messages: MPTP triggers the presentation of proteins decorated with sLeX in mouse brain.MPTP triggers the expression of sLeX rate-limiting enzyme FUT 7 in striatum.sLeX is expressed in neurons, including dopaminergic neurons, and microglia.sLeX in the brain may have a role in neuronal signalling and immunomodulation.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitRUNNunes, Maria JoãoCarvalho, Andreia NevesRosa, Alexandra I.Videira, Paula A.Gama, Maria JoãoRodrigues, ElsaCastro-Caldas, Margarida2024-04-26T23:48:27Z2024-032024-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://hdl.handle.net/10362/166668eng0946-2716PURE: 82549109https://doi.org/10.1007/s00109-023-02415-3info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-07-08T01:33:36Zoai:run.unl.pt:10362/166668Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:51:40.381587Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| dc.title.none.fl_str_mv |
Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease |
| title |
Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease |
| spellingShingle |
Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease Nunes, Maria João Glycosylation MPTP Parkinson’s disease Sialyl Lewis X Molecular Medicine Drug Discovery Genetics(clinical) |
| title_short |
Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease |
| title_full |
Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease |
| title_fullStr |
Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease |
| title_full_unstemmed |
Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease |
| title_sort |
Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease |
| author |
Nunes, Maria João |
| author_facet |
Nunes, Maria João Carvalho, Andreia Neves Rosa, Alexandra I. Videira, Paula A. Gama, Maria João Rodrigues, Elsa Castro-Caldas, Margarida |
| author_role |
author |
| author2 |
Carvalho, Andreia Neves Rosa, Alexandra I. Videira, Paula A. Gama, Maria João Rodrigues, Elsa Castro-Caldas, Margarida |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
DCV - Departamento de Ciências da Vida UCIBIO - Applied Molecular Biosciences Unit RUN |
| dc.contributor.author.fl_str_mv |
Nunes, Maria João Carvalho, Andreia Neves Rosa, Alexandra I. Videira, Paula A. Gama, Maria João Rodrigues, Elsa Castro-Caldas, Margarida |
| dc.subject.por.fl_str_mv |
Glycosylation MPTP Parkinson’s disease Sialyl Lewis X Molecular Medicine Drug Discovery Genetics(clinical) |
| topic |
Glycosylation MPTP Parkinson’s disease Sialyl Lewis X Molecular Medicine Drug Discovery Genetics(clinical) |
| description |
Publisher Copyright: © 2024, The Author(s). |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024-04-26T23:48:27Z 2024-03 2024-03-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/166668 |
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http://hdl.handle.net/10362/166668 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
0946-2716 PURE: 82549109 https://doi.org/10.1007/s00109-023-02415-3 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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13 application/pdf |
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Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
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Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia |
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info@rcaap.pt |
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