References of "Boyd, Olga 50001024"
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See detailCharacterization of Differentiated SH-SY5Y as Neuronal Screening Model Reveals Increased Oxidative Vulnerability
Antony, Paul UL; Forster, Julia UL; Köglsberger, Sandra UL et al

in Journal of Biomolecular Screening : The Official Journal of the Society for Biomolecular Screening (2016)

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See detailPlatelet mitochondrial membrane potential in Parkinson's disease.
Antony, Paul UL; Boyd, Olga UL; Trefois, Christophe UL et al

in Annals of clinical and translational neurology (2015), 2(1), 67-73

OBJECTIVE: Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease (IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial ... [more ▼]

OBJECTIVE: Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease (IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial function at the level of selected enzymatic activities in peripheral tissues have produced conflicting data. We considered the electron transport chain as a complex system with mitochondrial membrane potential as an integrative indicator for mitochondrial fitness. METHODS: Twenty-five IPD patients (nine females; mean disease duration, 6.2 years) and 16 healthy age-matched controls (12 females) were recruited. Live platelets were purified using magnetic-activated cell sorting (MACS) and single-cell data on mitochondrial membrane potential (Deltapsi) were measured by cytometry and challenged with a protonophore agent. RESULTS: Functional mitochondrial membrane potential was detected in all participants. The challenge test reduced the membrane potential in all IPD patients and controls (P < 0.001). However, the response to the challenge was not significantly different between patients and controls. INTERPRETATION: While the reported protonophore challenge assay is a valid marker of overall mitochondrial function in live platelets, intact mitochondrial membrane potential in platelets derived from IPD patients suggests that presumed mitochondrial enzymatic deficiencies are compensable in this cell type. In consequence, mitochondrial membrane potential in platelets cannot be used as a diagnostic biomarker for nonstratified IPD but should be further explored in potential Parkinson's disease subtypes and tissues with higher energy demands. [less ▲]

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See detailSystems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson’s disease
Krishna, Abhimanyu UL; Biryukov, Maria UL; Trefois, Christophe UL et al

in BMC Genomics (2014), 15(1154),

Background: The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often ... [more ▼]

Background: The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often used as a cellular model for Parkinson’s disease, the relevance of this cellular model in the context of Parkinson’s disease (PD) and other neurodegenerative diseases has not yet been systematically evaluated. Results: We have used a systems genomics approach to characterize the SH-SY5Y cell line using whole-genome sequencing to determine the genetic content of the cell line and used transcriptomics and proteomics data to determine molecular correlations. Further, we integrated genomic variants using a network analysis approach to evaluate the suitability of the SH-SY5Y cell line for perturbation experiments in the context of neurodegenerative diseases, including PD. Conclusions: The systems genomics approach showed consistency across different biological levels (DNA, RNA and protein concentrations). Most of the genes belonging to the major Parkinson’s disease pathways and modules were intact in the SH-SY5Y genome. Specifically, each analysed gene related to PD has at least one intact copy in SH-SY5Y. The disease-specific network analysis approach ranked the genetic integrity of SH-SY5Y as higher for PD than for Alzheimer’s disease but lower than for Huntington’s disease and Amyotrophic Lateral Sclerosis for loss of function perturbation experiments. [less ▲]

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See detailDifferentiated SH-SY5Y Cells as PD Model for Mitochondrial Dysfunction: From Whole Genome Sequencing to an Educated Design of High-Throughput Experiments
Antony, Paul UL; Krishna, Abhimanyu UL; May, Patrick UL et al

Poster (2013)

Objectives: Mitochondrial dysfunction is a cellular hallmark of Parkinson's disease (PD) and energetic stress of dopaminergic neurons appears to be a physiological risk factor for mitochondrial ... [more ▼]

Objectives: Mitochondrial dysfunction is a cellular hallmark of Parkinson's disease (PD) and energetic stress of dopaminergic neurons appears to be a physiological risk factor for mitochondrial dysfunction. It is however challenging to assess the high variety of factors regulating mitochondrial physiology in living neurons in a high throughput manner. To overcome this bottleneck, we established an analysis platform, using the neuroblastoma cell line SH-SY5Y. For the first time ever we have characterized the SH-SY5Y cell line in an integrated whole genome, transcriptome, and proteome approach. In addition, we show that neuronal differentiation improves the physiological properties of this experimental model for studying mitochondrial dysfunction in PD. Methods: Whole genome sequencing, RNA-Seq, qRT-PCR, MS, FRET using Voltage sensing proteins, Immunofluorescence, cytometry, and live cell imaging. Results: The integrated molecular characterization of SH-SY5Y uncovers the level of molecular network integrity and hence the relevance of this cell line for targeted studies in selected molecular processes. Furthermore, we dissect changes in mitochondrial and energetic stress factors during the process of neuronal differentiation. Conclusions: In terms of both morphology and energetic stress response, differentiated SH-SY5Y cells are more similar to dopaminergic neurons than their undifferentiated precursors. Thanks to dividing progenitors and the short duration of differentiation, combined with the use of specific endpoints analysed with high-content microscopy, our platform paves the route for high throughput experiments on a neuronal cell culture model for PD. Our genomic characterization and expression profiling of SH-SY5Y cells furthermore helps guiding the experimental design and interpretation of such studies. [less ▲]

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See detailAnalysis of critical transitions in Parkinson's disease
Trefois, Christophe UL; Antony, Paul UL; Baumuratov, Aidos UL et al

Poster (2011, December 12)

Background Parkinson’s disease is the most common neurodegenerative movement disorder and is clinically characterized by resting tremor, bradykinesia and cogwheel rigidity. The disease affects 1-2% of the ... [more ▼]

Background Parkinson’s disease is the most common neurodegenerative movement disorder and is clinically characterized by resting tremor, bradykinesia and cogwheel rigidity. The disease affects 1-2% of the global population with prevalence in the people above 65 years of age. The main pathological hallmark of Parkinson’s disease is a progressive loss of dopaminergic neurons in the substantia nigra. Therefore, one important challenge is to improve the understanding of regime shifts between health and disease states. Improving predictions of critical transitions triggering the onset of parkinsonian phenotypes could contribute to the improvement of preventive treatments. Methods Based on cellular models, we will use the mathematical concept of critical transitions to create a toolbox for potentially predicting tipping points towards cellular Parkinson’s disease phenotypes, e.g. mitochondrial dysfunction. Experimentally, we will induce and analyze potential critical transitions in the SH-SY5Y cell line. To do this, we will apply Parkinson’s disease relevant chemical and genetic perturbations and analyze multiple scales of the resulting temporal system behavior. We will combine high content imaging with genetic and biochemical data. A significant informatics challenge arises from the aim to perform the analysis of high time-resolved 3D imaging data. We are therefore developing an automated image analysis pipeline that relies on latest technologies and techniques, such as 3D deconvolution and 3D particle tracking. This pipeline will be applied to study parameters, such as mitochondrial dynamics, which include for instance velocity, morphology, and spatial organization. [less ▲]

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