IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A functional miss-expression screen uncovers a role for enabled in progressive neurodegeneration.
Autor/es:
C REZÁVAL AND MF CERIANI
Lugar:
Cold Spring Harbor Laboratories
Reunión:
Congreso; Neurobioloogy of Drosophila; 2007
Resumen:
In recent years Drosophila has been established as a genetic model to study the molecular basis of neurodegenerative diseases. So far most efforts have been directed towards the expression of mutated genes that are known to be involved in human disease. We hypothesize that altered levels of expression of genes relevant for neuronal function and homeostasis might render a defective behavior. Behavioral defects that become apparent in aged but not in young flies should uncover genes with a potential involvement in neurodegeneration.  To test this hypothesis we have carried out a miss-expression screen based on an automated behavioral assay to quantitatively assess circadian locomotor activity in young and aged Drosophila individuals. We have identified several loci that distinctively affect this behavior in older flies. One of the interesting candidates showing progressive arrhythmicity in the activity paradigm resulted in a GAL4-mediated reduction in the endogenous levels of enabled (ena). ena miss-expression not only triggered degeneration of retinal structures but also gave rise to neuronal death in specific regions of the adult brain. The potential mechanisms underlying this phenomenon are currently under investigation. Given the increasing interest in understanding neurological disorders, progress in this model system is likely to have a broad impact, ultimately assisting in the dissection of relevant pathways to neurodegeneration in the mammalian brain.