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Istituto sull'inquinamento atmosferico

Torna all'elenco Contributi in rivista anno 2014

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Potential involvement of GRIN2B encoding the NMDA receptor subunit NR2B in the spectrum of Alzheimer's disease

Anno di pubblicazione: 2014

Formato: Elettronico Cartaceo

Autori: Andreoli, Virginia; De Marco, Elvira Valeria; Trecroci, Francesca; Cittadella, Rita; Di Palma, Gemma; Gambardella, Antonio

Affiliazioni autori: Consiglio Nazionale delle Ricerche (CNR); Magna Graecia University of Catanzaro

Autori CNR:


Abstract: Increasing evidence links dysregulation of NR2B-containing N-methyl-d-aspartate receptor remodelling and trafficking to Alzheimer's disease (AD). This theme offers the possibility that the GRIN2B gene, encoding this selective NR2B subunit, represents a potential molecular modulating factor for this disease. Based on this hypothesis, we carried out a mutation scanning of exons and flanking regions of GRIN2B in a well-characterized cohort of AD patients, recruited from Southern Italy. A "de novo" p.K1293R mutation, affecting a highly conserved residue of the protein in the C-terminal domain, was observed for the first time in a woman with familial AD, as the only genetic alteration of relevance. Moreover, an association study between the other detected sequence variants and AD was performed. In particular, the study was focused on five identified single nucleotide polymorphisms: rs7301328, rs1805482, rs3026160, rs1806191 and rs1806201, highlighting a significant contribution from the GRIN2B rs1806201 T allele towards disease susceptibility [adjusted odds ratio (OR) = 1.92, 95% confidence interval (CI) 1.40-2.63, p < 0.001, after correction for sex, age, and APOE epsilon 4 genotype]. This was confirmed by haplotype analysis that identified a specific haplotype, carrying the rs1806201 T allele (CCCTC), over-represented in patients versus controls (adjusted OR = 6.03; p < 0.0001). Although the pathogenic role of the GRIN2B-K1293R mutation in AD is not clear, our data advocate that genetic variability in the GRIN2B gene, involved in synaptic functioning, might provide valuable insights into disease pathogenesis, continuing to attract significant attention in biomedical research on its genetic and functional role.

Pagine da: 533

Pagine a: 542

Pagine totali: 10


Journal of neural transmission Springer
Paese di pubblicazione: Austria
Lingua: multilingue
ISSN: 0300-9564

Numero volume: 121

Numero fascicolo: 5

DOI: 10.1007/s00702-013-1125-7

Indicizzato da: ISI Web of Science (WOS) [000334933500010]

Parole chiave:

  • Alzheimer's dementia
  • Excitotoxicity
  • Glutamate
  • N-methyl-D-aspartate receptors GRIN2B gene
  • Regulation of synaptogenesis

Strutture CNR:


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