TY - JOUR
T1 - Altered expression of Sialyl Lewis X in experimental models of Parkinson’s disease
AU - Nunes, Maria João
AU - Carvalho, Andreia Neves
AU - Rosa, Alexandra I.
AU - Videira, Paula A.
AU - Gama, Maria João
AU - Rodrigues, Elsa
AU - Castro-Caldas, Margarida
N1 - Funding Information:
info:eu-repo/grantAgreement/FCT/Projetos de Investigação Científica e Desenvolvimento Tecnológico - 2012/PTDC%2FNEU-NMC%2F0248%2F2012/PT#
info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F72891%2F2010/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FDTP%2F04138%2F2013/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT#
Publisher Copyright:
© 2024, The Author(s).
PY - 2024/3
Y1 - 2024/3
N2 - 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.
AB - 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.
KW - Glycosylation
KW - MPTP
KW - Parkinson’s disease
KW - Sialyl Lewis X
UR - http://www.scopus.com/inward/record.url?scp=85181870597&partnerID=8YFLogxK
U2 - 10.1007/s00109-023-02415-3
DO - 10.1007/s00109-023-02415-3
M3 - Article
C2 - 38197965
AN - SCOPUS:85181870597
SN - 0946-2716
VL - 102
SP - 365
EP - 377
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 3
ER -