Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptional profiling of human olfactory neurosphere-derived cell lines from healthy and idiopathic Parkinsons disease individuals.

ABSTRACT: The human olfactory epithelium represents a readily accessible source of adult neural cell types which can be propagated in vitro. We have used this feature to establish olfactory neurosphere-derived (hONS) cells lines from patients with idiopathic Parkinson's disease (PD) and healthy controls. We interrogated several metabolic activities of hONS cells from PD patients and detected significantly decreased levels of reduced glutathione and MTS [3- (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] metabolism. Both were decreased to approximately 80% of control donor hONS cell levels. These decreases did not correlate with any other known parameter, such as donor age or gender nor with the number of passages in vitro. Therefore we conclude that the differences are either symptomatic of PD or reflect an underlying predisposition for PD. Transcriptomic analysis identified the xenobiotic and anti-oxidant pathways, mediated by the aryl hydrocarbon receptor and NRF2, respectively, as significantly dysregulated in PD hONS cells. We show here that activation of the NRF2 pathway, by ectopic L-sulforaphane treatment, increased total glutathione and MTS metabolism levels to control-donor hONS cell levels in 12 of 14 hONS cell lines established from 14 individual donors with idiopathic PD. The importance of our results is three-fold. Firstly, they corroborated data obtained from in vivo and other in vitro cell models but uniquely on varied human genetic backgrounds. Secondly, they demonstrate that cells from PD patients are responsive to NRF2 pathway activation. Finally, they suggest that the dysregulation of the NRF2 pathway is not merely symptomatic of PD but may be a contributing factor.

ORGANISM(S): Homo sapiens

SUBMITTER: Nicholas Matigian

PROVIDER: E-TABM-879 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

NRF2 activation restores disease related metabolic deficiencies in olfactory neurosphere-derived cells from patients with sporadic Parkinson's disease.

Cook Anthony L AL Vitale Alejandra M AM Ravishankar Sugandha S Matigian Nicholas N Sutherland Greg T GT Shan Jiangou J Sutharsan Ratneswary R Perry Chris C Silburn Peter A PA Mellick George D GD Whitelaw Murray L ML Wells Christine A CA Mackay-Sim Alan A Wood Stephen A SA

PloS one 20110701 7

<h4>Background</h4>Without appropriate cellular models the etiology of idiopathic Parkinson's disease remains unknown. We recently reported a novel patient-derived cellular model generated from biopsies of the olfactory mucosa (termed olfactory neurosphere-derived (hONS) cells) which express functional and genetic differences in a disease-specific manner. Transcriptomic analysis of Patient and Control hONS cells identified the NRF2 transcription factor signalling pathway as the most differential ...[more]

PMID: 21747966

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Dataset Information

Transcriptional profiling of human olfactory neurosphere-derived cell lines from healthy and idiopathic Parkinsons disease individuals.

Publications

NRF2 activation restores disease related metabolic deficiencies in olfactory neurosphere-derived cells from patients with sporadic Parkinson's disease.

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