Imperial College London
Professor Dominic Withers

ProfessorDominicWithers

Faculty of Medicine, Institute of Clinical Sciences

Clinical Chair in Diabetes & Endocrinology
 
 
 
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Contact

 

d.withers

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Irvine:2019:10.1038/s41598-019-52391-3,
author = {Irvine, E and Katsouri, L and Plattner, F and Al-Qassab, H and Al-Nackkash, R and Bates, G and Withers, D},
doi = {10.1038/s41598-019-52391-3},
journal = {Scientific Reports},
title = {Genetic deletion of S6k1 does not rescue the phenotypic deficits observed in the R6/2 mouse model of Huntington’s disease},
url = {http://dx.doi.org/10.1038/s41598-019-52391-3},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Huntington’s disease (HD) is a fatal inherited autosomal dominant neurodegenerative disorder caused by an expansion in the number of CAG trinucleotide repeats in the huntingtin gene. The disease is characterized by motor, behavioural and cognitive symptoms for which at present there are no disease altering treatments. It has been shown that manipulating the mTOR (mammalian target of rapamycin) pathway using rapamycin or its analogue CCI-779 can improve the cellular and behavioural phenotypes of HD models. Ribosomal protein S6 kinase 1 (S6K1) is a major downstream signalling molecule of mTOR, and its activity is reduced by rapamycin suggesting that deregulation of S6K1 activity may be beneficial in HD. Furthermore, S6k1 knockout mice have increased lifespan and improvement in age-related phenotypes. To evalute the potential benefit of S6k1 loss on HD-related phenotypes, we crossed the R6/2 HD model with the long-lived S6k1 knockout mouse line. We found that S6k1 knockout does not ameliorate behavioural or physiological phenotypes in the R6/2 mouse model. Additionally, no improvements were seen in brain mass reduction or huntingtin protein aggregate levels. Therefore, these results suggest that while a reduction in S6K1 signalling has beneficial effects on ageing it is unlikely to be a therapeutic strategy for HD patients.
AU  - Irvine,E
AU  - Katsouri,L
AU  - Plattner,F
AU  - Al-Qassab,H
AU  - Al-Nackkash,R
AU  - Bates,G
AU  - Withers,D
DO  - 10.1038/s41598-019-52391-3
PY  - 2019///
SN  - 2045-2322
TI  - Genetic deletion of S6k1 does not rescue the phenotypic deficits observed in the R6/2 mouse model of Huntington’s disease
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-52391-3
UR  - http://hdl.handle.net/10044/1/74519
VL  - 9
ER  -
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