Imperial College London
Portrait Picture

DrPanteleimonTakis

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Associate
 
 
 
//

Contact

 

p.takis Website

 
 
//

Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Lima:2021:10.1172/jci.insight.146934,
author = {Lima, Cunha D and Richardson, R and Tracey-White, D and Abbouda, A and Mitsios, A and Horneffer-van, der Sluis V and Takis, P and Owen, N and Skinner, J and Welch, AA and Moosajee, M},
doi = {10.1172/jci.insight.146934},
journal = {JCI Insight},
title = {REP1-deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia},
url = {http://dx.doi.org/10.1172/jci.insight.146934},
volume = {6},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Choroideremia (CHM) is a X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). Loss of functional REP1 leads to the accumulation of unprenylated Rab proteins and defective intracellular protein trafficking, the putative cause for photoreceptor, retinal pigment epithelium (RPE) and choroidal degeneration. CHM is ubiquitously expressed, but adequate prenylation is considered to be achieved, outside the retina, through the isoform REP2. Recently, the possibility of systemic features in CHM has been debated, hence, in this study whole metabolomic analysis of plasma samples from 25 CHM patients versus age and gender matched controls was performed. Results showed plasma alterations in oxidative stress-related metabolites, coupled with alterations in tryptophan metabolism leading to significantly raised serotonin levels. Lipid metabolism was disrupted with decreased branched fatty acids and acylcarnitines, suggestive of dysfunctional lipid oxidation, and imbalances of several sphingolipids and glycerophospholipids. Targeted lipidomics of the chmru848 zebrafish provided further evidence for dysfunction, with the use of Fenofibrates over Simvastatin circumventing the prenylation pathway to improve the lipid profile and increase survival. This study provides strong evidence for systemic manifestations of CHM and proposes novel pathomechanisms and targets for therapeutic consideration.
AU  - Lima,Cunha D
AU  - Richardson,R
AU  - Tracey-White,D
AU  - Abbouda,A
AU  - Mitsios,A
AU  - Horneffer-van,der Sluis V
AU  - Takis,P
AU  - Owen,N
AU  - Skinner,J
AU  - Welch,AA
AU  - Moosajee,M
DO  - 10.1172/jci.insight.146934
PY  - 2021///
SN  - 2379-3708
TI  - REP1-deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia
T2  - JCI Insight
UR  - http://dx.doi.org/10.1172/jci.insight.146934
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33755601
UR  - https://insight.jci.org/articles/view/146934
UR  - http://hdl.handle.net/10044/1/87634
VL  - 6
ER  -
Download