دورية أكاديمية
Altered expression of Sialyl Lewis X in experimental models of Parkinson's disease.
العنوان: | Altered expression of Sialyl Lewis X in experimental models of Parkinson's disease. |
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المؤلفون: | Nunes MJ; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal., Carvalho AN; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal., Rosa AI; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal., Videira PA; Department of Life Sciences, UCIBIO, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. p.videira@fct.unl.pt.; CDG & Allies - Professionals and Patient Associations International Network (CDG & Allies - PPAIN), NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. p.videira@fct.unl.pt., Gama MJ; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal., Rodrigues E; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal., Castro-Caldas M; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal. mcastrocaldas@ff.ulisboa.pt.; Department of Life Sciences, UCIBIO, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. mcastrocaldas@ff.ulisboa.pt. |
المصدر: | Journal of molecular medicine (Berlin, Germany) [J Mol Med (Berl)] 2024 Mar; Vol. 102 (3), pp. 365-377. Date of Electronic Publication: 2024 Jan 10. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Springer International Country of Publication: Germany NLM ID: 9504370 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1440 (Electronic) Linking ISSN: 09462716 NLM ISO Abbreviation: J Mol Med (Berl) Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Berlin : Springer International Original Publication: Berlin : Springer, c1994- |
مواضيع طبية MeSH: | Parkinson Disease*/genetics , Parkinson Disease*/metabolism, Animals ; Mice ; Sialyl Lewis X Antigen ; Inflammation ; Brain/metabolism ; Models, Theoretical ; Disease Models, Animal ; Mice, Inbred C57BL |
مستخلص: | 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. (© 2024. The Author(s).) |
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معلومات مُعتمدة: | PTDC/NEU-NMC/0248/2012 Fundação para a Ciência e a Tecnologia; SFRH/BPD/72891/2010 Fundação para a Ciência e a Tecnologia; UID/DTP/04138/2013 Fundação para a Ciência e a Tecnologia; UIDP/04378/2020 Fundação para a Ciência e a Tecnologia; UIDB/04378/2020 Fundação para a Ciência e a Tecnologia |
فهرسة مساهمة: | Keywords: Glycosylation; MPTP; Parkinson’s disease; Sialyl Lewis X |
المشرفين على المادة: | 0 (Sialyl Lewis X Antigen) |
تواريخ الأحداث: | Date Created: 20240110 Date Completed: 20240221 Latest Revision: 20240522 |
رمز التحديث: | 20240522 |
مُعرف محوري في PubMed: | PMC10879467 |
DOI: | 10.1007/s00109-023-02415-3 |
PMID: | 38197965 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1432-1440 |
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DOI: | 10.1007/s00109-023-02415-3 |