INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
artículos
Título:
ENA/VASP downregulation triggers cell death by impairing axonal maintenance in hippocampal neurons.
Autor/es:
FRANCO, L., REZÁVAL, C., CÁCERES, A., SCHINDER, A., CERIANI, M. F.
Revista:
MOLECULAR AND CELLULAR NEUROSCIENCES.
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 2010 vol. 44 p. 154 - 164
ISSN:
1044-7431
Resumen:
Neurodegenerative diseases encompass a broad variety of motor and cognitive disorders that areaccompanied by death of specific neuronal populations or brain regions. Cellular and molecular mechanisms underlying these complex disorders remain largely unknown. In a previous work we searched for novel Drosophila genes relevant for neurodegeneration and singled out enabled (ena), which encodes a protein involved in cytoskeleton remodeling. To extend our understanding on the mechanisms of ENA-triggered degeneration we now investigated the effect of silencing ena ortholog genes in mouse hippocampal neurons. We found that ENA/VASP downregulation led to neurite retraction and concomitant neuronal cell death through an apoptotic pathway. Remarkably, this retraction initially affected the axonal structure, showing no effect on dendrites. Reduction in ENA/VASP levels blocked the neuritogenic effect of a specific RhoA kinase (ROCK) inhibitor, thus suggesting that these proteins could participate in the Rho-signaling pathway. Altogether these observations demonstrate that ENA/VASP proteins are implicated in the establishmentand maintenance of the axonal structure and that a change on their expression levels triggers neuronal degeneration.