Fahlbusch, Christiane

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Journal of Parkinson's Disease"],["dc.bibliographiccitation.lastpage","26"],["dc.contributor.author","Brás, Inês C."],["dc.contributor.author","Khani, Mohammad H."],["dc.contributor.author","Vasili, Eftychia"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Parfentev, Iwan"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Fahlbusch, Christiane"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2022-11-01T10:17:15Z"],["dc.date.available","2022-11-01T10:17:15Z"],["dc.date.issued","2022"],["dc.description.abstract","Background: Various cellular pathways have been implicated in the transfer of disease-related proteins between cells, contributing to disease progression and neurodegeneration. However, the overall effects of protein transfer are still unclear. Objective: Here, we performed a systematic comparison of basic molecular mechanisms involved in the release of alpha-synuclein, Tau, and huntingtin, and evaluated functional effects upon internalization by receiving cells. Methods: Evaluation of protein release to the extracellular space in a free form and in extracellular vesicles using an optimized ultracentrifugation protocol. The extracellular effects of the proteins and extracellular vesicles in primary neuronal cultures were assessed using multi-channel electrophysiological recordings combined with a customized spike sorting framework. Results: We demonstrate cells differentially release free-forms of each protein to the extracellular space. Importantly, neuronal activity is distinctly modulated upon protein internalization in primary cortical cultures. In addition, these disease-related proteins also occur in extracellular vesicles, and are enriched in ectosomes. Internalization of ectosomes and exosomes by primary microglial or astrocytic cells elicits the production of pro-inflammatory cytokines, and modifies spontaneous electrical activity in neurons. Objective: Overall, our study demonstrates that released proteins can have detrimental effects for surrounding cells, and suggests protein release pathways may be exploited as therapeutic targets in different neurodegenerative diseases."],["dc.identifier.doi","10.3233/JPD-223516"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116767"],["dc.notes.intern","DOI-Import GROB-605"],["dc.relation.eissn","1877-718X"],["dc.relation.issn","1877-7171"],["dc.title","Molecular Mechanisms Mediating the Transfer of Disease-Associated Proteins and Effects on Neuronal Activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]