Academic Journal
Glycation modulates glutamatergic signaling and exacerbates Parkinson’s disease-like phenotypes
| العنوان: | Glycation modulates glutamatergic signaling and exacerbates Parkinson’s disease-like phenotypes |
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| المؤلفون: | Chegão, Ana, Guarda, Mariana, Alexandre, Bruno M., Shvachiy, Liana, Temido Ferreira, Mariana, Marques-Morgado, Inês, Fernandes Gomes, Bárbara, Matthiesen, Rune, Lopes, Luisa V., Florindo, Pedro R., Gomes, Ricardo A., Gomes-Alves, Patrícia, Coelho, Joana E, Outeiro, Tiago, Vicente Miranda, Hugo |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2022 |
| المجموعة: | Universidade de Lisboa: repositório.UL |
| الوصف: | © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. ; Alpha-synuclein (aSyn) is a central player in the pathogenesis of synucleinopathies due to its accumulation in typical protein aggregates in the brain. However, it is still unclear how it contributes to neurodegeneration. Type-2 diabetes mellitus is a risk factor for Parkinson's disease (PD). Interestingly, a common molecular alteration among these disorders is the age-associated increase in protein glycation. We hypothesized that glycation-induced neuronal dysfunction is a contributing factor in synucleinopathies. Here, we dissected the impact of methylglyoxal (MGO, a glycating agent) in mice overexpressing aSyn in the brain. We found that MGO-glycation potentiates motor, cognitive, olfactory, and colonic dysfunction in aSyn transgenic (Thy1-aSyn) mice that received a single dose of MGO via intracerebroventricular injection. aSyn accumulates in the midbrain, striatum, and prefrontal cortex, and protein glycation is increased in the cerebellum and midbrain. SWATH mass spectrometry analysis, used to quantify changes in the brain proteome, revealed that MGO mainly increase glutamatergic-associated proteins in the midbrain (NMDA, AMPA, glutaminase, VGLUT ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2373-8057 |
| Relation: | info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FNEU-OSD%2F5644%2F2014/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04462%2F2020/PT; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04462%2F2020/PT; info:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F136863%2F2018/PT; info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F143286%2F2019/PT; https://www.nature.com/npjparkd/; NPJ Parkinsons Dis. 2022 Apr 25;8(1):51; http://hdl.handle.net/10451/52572 |
| DOI: | 10.1038/s41531-022-00314-x |
| الاتاحة: | http://hdl.handle.net/10451/52572 https://doi.org/10.1038/s41531-022-00314-x |
| Rights: | openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.3C4CF61B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 23738057 |
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| DOI: | 10.1038/s41531-022-00314-x |