Human microglia in Parkinson’s disease pathology
The doctoral research aims to elucidate how human microglia uptake and process aggregated alpha synuclein fibrils when exposed to inflammatory environment, modelling sporadic Parkinson’s disease. Combining omics (transcriptomics, metabolomics, and lipidomics) together with functional assays (e.g. live-cell imaging, cytokine bead array) and traditional gene and protein analysis (e.g. ICC,WB, qPCR) we aim to get an multifaceted overwiew on the effects. End point is to observe the impact of microglial secretions on the wellbeing of iPSC-derived dopaminergic neurons.
Figure 1. Representative images from IFNγ immunostimulated microglia processing alpha synuclein preformed fibrils (aSyn PFFs). A. Live-imaging from the phagocytosis of ATTO-labeled aSyn PFFs. Scale bar 100µm. B. Confocal image of microglia stained with total aSyn (red) and lysosomal-associated membrane protein 1, LAMP1 (green). Scale bar 5µm.
Publications
Niskanen, J, Peltonen, S, Ohtonen, S, Fazaludeen, M.F, Luk, K.C, Giudice, L, Koistinaho, J, Malm, T, Goldsteins, G, Albert, K, Lehtonen, Š. 2024 Uptake of alpha-synuclein preformed fibrils is suppressed by inflammation and induces an aberrant phenotype in human microglia. GLIA, 24626,1098-1136, https://doi.org/10.1002/glia.24626
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. https://doi.org/10.3390/biomedicines10102649
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, 4334. https://doi.org/10.3390/ijms22094334
Holmqvist S*, Lehtonen Š*, Chumarina M, Puttonen KA, Azevedo C, Lebedeva O, Ruponen M, Oksanen M, Collin A, Goldwurm S, Meyer M, Lagarkova M, Kiselev S, Koistinaho J, Roybon L. 2016 Creation of a library of induced pluripotent stem cells from Parkinsonian patients. npj Parkinsonʼs disease 2:16009. * equal contribution https://doi.org/10.1038/npjparkd.2016.9