Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome

作者：Cortelazzo Alessio; De Felice Claudio^*; Guerranti Roberto; Signorini Cinzia; Leoncini Silvia; Pecorelli Alessandra; Scalabri Francesco; Madonna Michele; Filosa Stefania; Della Giovampaola Cinzia; Capone Antonietta; Durand Thierry; Mirasole Cristiana; Zolla Lello; Valacchi Giuseppe; Ciccoli Lucia; Guy Jacky; D'Esposito Maurizio; Hayek Joussef

来源：Neuroscience Research, 2016, 105: 28-34.

DOI：10.1016/j.neures.2015.10.002

• Protein glycosylation
• Neurological disorders
• Nucleotide pyrophosphatase
• Mecp2

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 methylCpG 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.

• 出版日期2016-4