Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/12620
Title: Rab11 rescues synaptic dysfunction and behavioural deficits in a Drosophila model of Huntington's disease.
Authors: Steinert, Joern R.
Campesan, Susanna
Richards, Paul
Kyriacou, Charalambos P.
Forsythe, Ian D.
Giorgini, Flaviano
First Published: 1-Jul-2012
Citation: Human Molecular Genetics, 2012, 21 (13), pp. 2912-2922
Abstract: Synapse abnormalities in Huntington's disease (HD) patients can precede clinical diagnosis and neuron loss by decades. The polyglutamine expansion in the huntingtin (htt) protein that underlies this disorder leads to perturbations in many cellular pathways, including the disruption of Rab11-dependent endosomal recycling. Impairment of the small GTPase Rab11 leads to the defective formation of vesicles in HD models and may thus contribute to the early stages of the synaptic dysfunction in this disorder. Here, we employ transgenic Drosophila melanogaster models of HD to investigate anomalies at the synapse and the role of Rab11 in this pathology. We find that the expression of mutant htt in the larval neuromuscular junction decreases the presynaptic vesicle size, reduces quantal amplitudes and evoked synaptic transmission and alters larval crawling behaviour. Furthermore, these indicators of early synaptic dysfunction are reversed by the overexpression of Rab11. This work highlights a potential novel HD therapeutic strategy for early intervention, prior to neuronal loss and clinical manifestation of disease.
DOI Link: 10.1093/hmg/dds117
ISSN: 0964-6906
eISSN: 1460-2083
Links: http://hdl.handle.net/2381/12620
http://hmg.oxfordjournals.org/content/21/13/2912
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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