Imperial College London
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ProfessorHectorKeun

Faculty of Medicine, Department of Surgery & Cancer

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)20 7594 3161h.keun

 
 
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Location

 

officesInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Valbuena:2015:10.1007/s12035-015-9165-7,
author = {Valbuena, GN and Rizzardini, M and Cimini, S and Siskos, AP and Bendotti, C and Cantoni, L and Keun, HC},
doi = {10.1007/s12035-015-9165-7},
journal = {Molecular Neurobiology},
pages = {2222--2240},
title = {Metabolomic Analysis Reveals Increased Aerobic Glycolysis and Amino Acid Deficit in a Cellular Model of Amyotrophic Lateral Sclerosis},
url = {http://dx.doi.org/10.1007/s12035-015-9165-7},
volume = {53},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Defects in energy metabolism are potential pathogenic mechanisms in amyotrophic lateral sclerosis (ALS), a rapidly fatal disease with no cure. The mechanisms through which this occurs remain elusive and their understanding may prove therapeutically useful. We used metabolomics and stable isotope tracers to examine metabolic changes in a well-characterized cell model of familial ALS, the motor neuronal NSC-34 line stably expressing human wild-type Cu/Zn superoxide dismutase (wtSOD1) or mutant G93A (G93ASOD1). Our findings indicate that wt and G93ASOD1 expression both enhanced glucose metabolism under serum deprivation. However, in wtSOD1 cells, this phenotype increased supply of amino acids for protein and glutathione synthesis, while in G93ASOD1 cells it was associated with death, aerobic glycolysis, and a broad dysregulation of amino acid homeostasis. Aerobic glycolysis was mainly due to induction of pyruvate dehydrogenase kinase 1. Our study thus provides novel insight into the role of deranged energy metabolism as a cause of poor adaptation to stress and a promoter of neural cell damage in the presence of mutant SOD1. Furthermore, the metabolic alterations we report may help explain why mitochondrial dysfunction and impairment of the endoplasmic reticulum stress response are frequently seen in ALS.
AU  - Valbuena,GN
AU  - Rizzardini,M
AU  - Cimini,S
AU  - Siskos,AP
AU  - Bendotti,C
AU  - Cantoni,L
AU  - Keun,HC
DO  - 10.1007/s12035-015-9165-7
EP  - 2240
PY  - 2015///
SN  - 1559-1182
SP  - 2222
TI  - Metabolomic Analysis Reveals Increased Aerobic Glycolysis and Amino Acid Deficit in a Cellular Model of Amyotrophic Lateral Sclerosis
T2  - Molecular Neurobiology
UR  - http://dx.doi.org/10.1007/s12035-015-9165-7
UR  - http://hdl.handle.net/10044/1/33943
VL  - 53
ER  -
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