In Greek myth, Proteus, a shapeshifter protector god, grew weary with age becoming the “Old Man of the Sea” Microglia, our brain’s shapeshifting immune guardians, act the same way; young cells shift form to defend and repair, but with age they falter, sometimes fusing into harmful forms. This decline fuels Parkinson’s disease, whose main risk factor is age. In our lab, we build an “ageing midbrain in a dish” to uncover its causes and test drugs that may slow its progression.
Impact
Parkinson’s disease (PD) affects over 10 million people, with risk increasing steeply with age. It can reduce independence making daily tasks like walking or working increasingly difficult. Our team is developing an “ageing midbrain in a dish” that incorporates multiple PD environmental stressors, with aging as the most prominent factor. This model allows us to test drugs that restore function or protect cells, aiming to slow disease and improve quality of life.
reNEW research
We have aged human stem-cell-derived midbrain neurons, astrocytes, and microglia in vitro, exposing them to additional environmental stressors such as mitochondrial dysfunction and inflammation to mimic Parkinson’s pathology. We have established a viable model with all three cell types, and we are now preparing a functional drug screen, using dopamine production as the key readout.
Image description
Microscopic view of the brain’s sentinels: human microglia grown from stem cells (90 days). Their membranes glow pink and nuclei grey, revealing the architecture of these vital cells.
Credits
Dr Nina-Lydia Kazakou, Postdoc, Josefine Rågård Christiansen, PhD Student Kirkeby Lab, reNEW Copenhagen.
