TY - JOUR
T1 - Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome
AU - Cortelazzo, Alessio
AU - De Felice, Claudio
AU - Guerranti, Roberto
AU - Signorini, Cinzia
AU - Leoncini, Silvia
AU - Pecorelli, Alessandra
AU - Scalabrì, Francesco
AU - Madonna, Michele
AU - Filosa, Stefania
AU - Della Giovampaola, Cinzia
AU - Capone, Antonietta
AU - Durand, Thierry
AU - Mirasole, Cristiana
AU - Zolla, Lello
AU - Valacchi, Giuseppe
AU - Ciccoli, Lucia
AU - Guy, Jacky
AU - D'Esposito, Maurizio
AU - Hayek, Joussef
PY - 2015/6/9
Y1 - 2015/6/9
N2 - Neurological disorders can be associated with protein glycosylation abnormalities. Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. Remarkable glycosylation pattern changes for a peculiar 50. kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. Glycosylation changes were rescued by selected brain Mecp2 reactivation. Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5.
AB - Neurological disorders can be associated with protein glycosylation abnormalities. Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. Remarkable glycosylation pattern changes for a peculiar 50. kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. Glycosylation changes were rescued by selected brain Mecp2 reactivation. Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5.
KW - Mecp2
KW - Neurological disorders
KW - Nucleotide pyrophosphatase
KW - Protein glycosylation
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U2 - 10.1016/j.neures.2015.10.002
DO - 10.1016/j.neures.2015.10.002
M3 - Article
AN - SCOPUS:84953325478
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
ER -