Longevity Briefs: Stem cell-derived artificial brain used to model Parkinson’s disease

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Parkinson’s disease (PD) is a neurodegenerative disease which primarily affects movement. It is caused by the declining function of dopaminergic neurons and accumulation of a-synuclein, resulting in tremors and mobility issues which are characteristic of PD.

Recent innovations in biomaterials and stem cell cultures have allowed the generation of complex three dimensional models, known as brain organoids. Compared to 2D cell cultures, brain organoids facilitate the formation of far more representative tissue architecture, neural circuits and complex neurological phenotypes to that of a real brain.

A cross-section of a brain organoid. Photograph: Madeline A Lancaster/IMBA/EPA

What did the researchers do: Using human stem cells, Kim et al. formed two midbrain organoids, one with a PD associated mutation, and one without, to serve as the control. By comparing the varying protein-protein interaction networks between the two organoids, the researchers reported, for the first time in a 3D culture, that the upregulation of the TXNIP gene is directly related to accumulation of a-synuclein.

Key takeaway(s) from this research: Using artificial 3D brain organoids to model disease is technology which is still very much in its infancy. However, as Kim et al., and many other researchers are proving, it is a technique that holds much promise for not only disease modelling, but also drug discovery and biomarker identification.