Selective cell vulnerability to alpha-synuclein: investigating the underlying region- and celltype- specific factors

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Investigating factors that make a specific region/cell type, particularly prone to each asynucleinopathy (PD, MSA, DLB). Reproduce each pathology on multiple models: cell cultures, human post-mortem brain tissue, mice, and minibrains of IPS cells. For these the following steps will apply: 1) initialscreening by correlative light-electron microscopy (CLEM) 2) structural characterization and time pattern identification bysuper resolution microscopy 3) microenvironment characterisation by scRNA seq, BioID, histology,immunohistochemistry, oxidative stress assays, calcium imaging 4) test the vulnerability criteria identified bysteps 1-3 both in vitro and in vivo (e.g. by CRISPR or biosensors).