Data di Pubblicazione:
2012
Citazione:
Contribution of serine racemase/d-serine pathway to neuronal apoptosis / S. Esposito, A. Pristerà, G. Maresca, S. Cavallaro, A. Felsani, F. Florenzano, L. Manni, M. Ciotti, L. Pollegioni, T. Borsello, N. Canu. - In: AGING CELL. - ISSN 1474-9718. - 11:4(2012 Aug), pp. 588-598.
Abstract:
Recent data indicate that age-related N-methyl-d-aspartate receptor (NMDAR) transmission impairment is correlated with the reduction in serine racemase (SR) expression and d-serine content. As apoptosis is associated with several diseases and conditions that generally occur with age, we investigated the modulation of SR/d-serine pathway during neuronal apoptosis and its impact on survival. We found that in cerebellar granule neurons (CGNs), undergoing apoptosis SR/d-serine pathway is crucially regulated. In the early phase of apoptosis, the expression of SR is reduced, both at the protein and RNA level through pathways, upstream of caspase activation, involving ubiquitin proteasome system (UPS) and c-Jun N-terminal kinases (JNKs). Forced expression of SR, together with treatment with NMDA and d-serine, blocks neuronal death, whereas pharmacological inhibition and Sh-RNA-mediated suppression of endogenous SR exacerbate neuronal death. In the late phase of apoptosis, the increased expression of SR contribute to the last, NMDAR-mediated, wave of cell death. These findings are relevant to our understanding of neuronal apoptosis and NMDAR activity regulation, raising further questions as to the role of SR/d-serine in those neuro-pathophysiological processes, such as aging and neurodegenerative diseases characterized by a convergence of apoptotic mechanisms and NMDAR dysfunction.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
animals; apoptosis; cell aging; cerebellum; in vitro techniques; JNK mitogen-activated protein kinases; neurons; proteasome endopeptidase complex; RNA, messenger; rna, small interfering; racemases and epimerases; rats; rats, wistar; receptors, n-methyl-d-aspartate; serine; signal transduction; stereoisomerism; animals; apoptosis; cell aging; cerebellum; in vitro techniques; JNK Mitogen-activated protein kinases; neurons; proteasome endopeptidase complex; RNA, messenger; rna, small interfering; racemases and epimerases; rats; rats, wistar; receptors, n-methyl-d-aspartate; serine; signal transduction; stereoisomerism
Elenco autori:
S. Esposito, A. Pristerà, G. Maresca, S. Cavallaro, A. Felsani, F. Florenzano, L. Manni, M. Ciotti, L. Pollegioni, T. Borsello, N. Canu
Link alla scheda completa: