The endoplasmic reticulum (ER) stress-mediated pathway is involved in a wide range of human neurodegenerative disorders. Hence, molecules that regulate the ER stress response represent potential candidates as drug targets to tackle these diseases. In previous studies we demonstrated that upon acetylation the reticulon-1C (RTN-1C) variant of the reticulon family leads to inhibition of histone deacetylase (HDAC) enzymatic activity and endoplasmic reticulum stress-dependent apoptosis. Here, by microarray analysis of the whole human genome we found that RTN-1C is able to specifically regulate gene expression, modulating transcript clusters which have been implicated in the onset of neurodegenerative disorders. Interestingly, we show that some of the identified genes were also modulated in vivo in a brain-specific mouse model overxpressing RTN-1C. These data provide a basis for further investigation of RTN-1C as a potential molecular target for use in therapy and as a specific marker for neurological diseases. (C) 2010 Elsevier Inc. All rights reserved.
Characterization of gene expression induced by RTN-1C in human neuroblastoma cells and in mouse brain
Nardacci R;
2010-01-01
Abstract
The endoplasmic reticulum (ER) stress-mediated pathway is involved in a wide range of human neurodegenerative disorders. Hence, molecules that regulate the ER stress response represent potential candidates as drug targets to tackle these diseases. In previous studies we demonstrated that upon acetylation the reticulon-1C (RTN-1C) variant of the reticulon family leads to inhibition of histone deacetylase (HDAC) enzymatic activity and endoplasmic reticulum stress-dependent apoptosis. Here, by microarray analysis of the whole human genome we found that RTN-1C is able to specifically regulate gene expression, modulating transcript clusters which have been implicated in the onset of neurodegenerative disorders. Interestingly, we show that some of the identified genes were also modulated in vivo in a brain-specific mouse model overxpressing RTN-1C. These data provide a basis for further investigation of RTN-1C as a potential molecular target for use in therapy and as a specific marker for neurological diseases. (C) 2010 Elsevier Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
