Altered expression of Sialyl Lewis X in experimental models of Parkinson's disease.
Glycosylation
MPTP
Parkinson’s disease
Sialyl Lewis X
Journal
Journal of molecular medicine (Berlin, Germany)
ISSN: 1432-1440
Titre abrégé: J Mol Med (Berl)
Pays: Germany
ID NLM: 9504370
Informations de publication
Date de publication:
10 Jan 2024
10 Jan 2024
Historique:
received:
16
05
2023
accepted:
22
12
2023
revised:
07
12
2023
medline:
10
1
2024
pubmed:
10
1
2024
entrez:
10
1
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38197965
doi: 10.1007/s00109-023-02415-3
pii: 10.1007/s00109-023-02415-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fundação para a Ciência e a Tecnologia
ID : PTDC/NEU-NMC/0248/2012
Organisme : Fundação para a Ciência e a Tecnologia
ID : SFRH/BPD/72891/2010
Organisme : Fundação para a Ciência e a Tecnologia
ID : UID/DTP/04138/2013
Organisme : Fundação para a Ciência e a Tecnologia
ID : UIDP/04378/2020
Organisme : Fundação para a Ciência e a Tecnologia
ID : UIDB/04378/2020
Informations de copyright
© 2024. The Author(s).
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