PD is the most common neurodegenerative movement disorder that affects more than 6 million people worldwide, and about 15,000 people in Finland. The motor symptoms are often preceded by non-motor symptoms and diagnosis is often made far too late when over 60% of dopaminergic neurons located in substantia nigra have already died. Despite decades of research, exact disease mechanisms are still unknown, and thus current treatments primarily rely on relieving symptoms.
In the project funded by Jane and Aatos Erkko Foundation, Lehtonen’s research group will focus on revealing the role of “non-cell-autonomous” mechanisms that involves the interaction of dopaminergic neurons with neighbouring glial cells such as astrocytes and microglia. The role of these glial cells in the pathogenesis of Parkinson’s disease is still poorly known, but there is growing evidence showing the contribution of these cells to non-cell-autonomous mechanisms in which neurodegeneration is strongly influenced by the toxicity of disease-specific proteins expressed in the glia. The researchers use pluripotent stem cell (iPSC) technology which allows the production of different brain cell types from patients’ fibroblasts. The interactions between different brain cell types are studied in several models, including 3D multicellular model and midbrain organoids.
“We have recently found out that astrocytes from PD patients produced significantly higher levels of α-synuclein, a protein that typically accumulates in dopaminergic neurons of PD patients’ brains, causing cell death. The PD patient astrocytes were also highly responsive to pro-inflammatory stimuli and more sensitive to inflammatory reactivation than control astrocytes,, says Lehtonen.
Lehtonen’s group will assess the role of microglia on astrocytic function and the consequence of glial interaction on dopaminergic neurons.
“Our study will provide new and more accurate information about how these two integral central nervous system glial cells contribute to PD pathogenesis and allow us to identify key therapeutic targets and pathways responsible for pathological glial phenotype in PD.”
Novel antibiotics can be effective against antibiotic-resistant bacteria
Professor Antti Poso at the School of Pharmacy has secured 291,000 euros of funding for a project seeking novel approaches for the treatment of infections caused by antibiotic-resistant bacteria. The antibiotic, to be developed in international collaboration, is based on the inhibition of the SurA protein, which plays an essential role in the formation of the bacterial cell wall.