Data di Pubblicazione:
2016
Citazione:
PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells / N. Marchesi, M. Amadio, C. Colombrita, S. Govoni, A. Ratti, A. Pascale. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 54:2(2016 Sep 06), pp. 535-547. [10.3233/JAD-160299]
Abstract:
Neuronal ELAV/Hu (nELAV) are RNA-binding proteins that mainly regulate gene expression by increasing the stability and/or translation rate of target mRNAs bearing ARE (adenine and uracil-rich elements) sequences. Among nELAV target transcripts there is ADAM10, an α-secretase involved in the non-amyloidogenic processing of the amyloid-β protein precursor (AβPP) which leads to the production of the neuroprotective sAβPPα peptide. The aim of this study was to evaluate if nELAV depletion affects ADAM10 expression in human SH-SY5Y neuroblastoma cells. We also studied the effects of Bryostatin-1, a molecule able to activate nELAV protein cascade. The specific HuD/nELAV gene silencing decreased both nELAV and ADAM10 protein contents; similar results were obtained by Aβ40 treatment in wild-type SH-SY5Y cells. In HuD-silenced cells, the exposure to Bryostatin-1 counteracted both nELAV and ADAM10 proteins downregulation, by restoring nELAV/ADAM10 basal levels. We also found that sAβPPα release, which seemed not to be compromised by Aβ40 challenge or HuD-silencing, was favored by Bryostatin-1. Overall, these findings strongly suggest that a deficiency in nELAV content negatively affects ADAM10 expression and may play a role in neurodegenerative diseases, which may benefit by molecules activating ELAV cascade.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
N. Marchesi, M. Amadio, C. Colombrita, S. Govoni, A. Ratti, A. Pascale
Link alla scheda completa: