A Novel Human Neuronal Cell Model to Study Iron Accumulation in Parkinson’s Disease

Kosha Mehta, Bushra, Y. Ahmed, Sebastien Farnaud

Research output: Contribution to journalArticle

Abstract

Objectives: With an estimated seven to ten million sufferers worldwide, Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. Progress in elucidating its causes has been slow, partly due to the lack of human-relevant models. Similarly, while the contribution of iron is increasingly advocated, identifying its role in disease progression remains challenging mainly due to the lack of valid model. In this study, we created Parkinson-like conditions in a human neuron model and conducted preliminary studies on iron-related parameters to assess whether these cells replicated iron accumulation observed in Parkinsonism. Methods: ReNcell VM (human neural progenitor) were differentiated into dopaminergic neurons (dDCNs) and treated with neurotoxin 6-hydroxy dopamine (100 μM) to mimic Parkinsonism. Total intracellular, mitochondrial and cytoplasmic iron was measured by ferrozine assay. Expression of iron-related genes TFRC, SLC40A1, HAMP and SLC25A37 were assessed through real-time PCR. Results: Data showed that the treated dDCNs accumulated iron over time and exceeded levels measured in untreated dDCNs by 2.5-fold at 48 h (p<0.02). Following the treatment, the treated cells showed lower expression of TFRC (p<0.05), but substantially higher mRNA expressions of SLC40A1 (9-fold; p<0.02) and HAMP (5.7-fold; p<0.05), along with higher intracellular iron (p<0.05). Higher iron accumulation in the mitochondria than cytosol (p<0.05), was also observed with increased expression of the mitochondrial iron-importer SLC25A37 (p=0.08). Conclusion: Our Parkinsonian model demonstrates iron accumulation and elevated HAMP expression as previously described in PD phenotype. The observed mitochondrial iron shuttling, which is proposed to be one of the primary contributors of oxidative stress in PD, calls for further investigation. The differences observed in distribution of iron in our human model and with the expression of major iron-related proteins, indicate that our model reproduces the disease state successfully, and suggests that further study could help in advancing our understanding of PD.
LanguageEnglish
Article number1000461
Number of pages5
JournalJournal of Alzheimer's Disease and Parkinsonism
Volume9
Issue number1
DOIs
Publication statusPublished - 11 Feb 2019

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Parkinson Disease
Iron
Dopaminergic Neurons
Parkinsonian Disorders
Ferrozine
Neurotoxins
Neurodegenerative Diseases
Cytosol
Disease Progression
Real-Time Polymerase Chain Reaction
Dopamine
Mitochondria
Oxidative Stress
Phenotype
Neurons
Messenger RNA

Bibliographical note

All works published by OMICS International are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the work provided the original work and source is appropriately cited.

Keywords

  • Parkinson's disease (PD)
  • Iron metabolism
  • Mitochondrial iron
  • Hepcidin
  • Neurons
  • Iron

Cite this

A Novel Human Neuronal Cell Model to Study Iron Accumulation in Parkinson’s Disease. / Mehta, Kosha; Ahmed, Bushra, Y.; Farnaud, Sebastien.

In: Journal of Alzheimer's Disease and Parkinsonism , Vol. 9, No. 1, 1000461, 11.02.2019.

Research output: Contribution to journalArticle

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