Microglia in α-synucleinopathies

Microglia have been observed near dying dopamine neurons in Parkinson’s disease postmortem brains. In addition to microglia’s immune response, they also phagocytose α-synuclein aggregates – indicating them as a key player in how the brain clears away debris and protects neurons. If we can leverage this response to increase protein clearance and reduce aggregates in dopamine neurons, this could be a useful therapeutic strategy. Using iPSCs to create human microglia cells has become a powerful tool to study how they function in health and disease. Human microglia were found to have differential gene expression compared to mouse and further, human microglia cultured in the dish were found to have different gene expression to those in the brain. Therefore, it is important to study these human cells in a whole brain environment so that they most closely resemble that in the human brain. 

In animal models using iPSCs, cells are derived from a donor’s somatic cells and differentiated to neuronal or glial precursors. These cells are then transplanted to the rodent brain and studied in situ in order to make a humanized model of disease.

Publications

Albert, K., Kälvälä, S., Hakosalo, V., Syvänen, V., Krupa, P., Niskanen, J., Peltonen, S., Sonninen, T.-M., & Lehtonen, Š. (2022) Cellular Models of Alpha-Synuclein Aggregation: What Have We Learned and Implications for Future Study. Biomedicines, 10, 2649. 

Albert, K., Niskanen, J., Kälvälä, S., & Lehtonen, Š. (2021) Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia. Int J Mol Sci, 22.