% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Klinkenberg:256448, author = {Klinkenberg, Michael and Helwig, Michael and Pinto-Costa, Rita and Rollar, Angela and Rusconi, Raffaella and Di Monte, Donato A and Ulusoy, Ayse}, title = {{I}nterneuronal {I}n {V}ivo {T}ransfer of {S}ynaptic {P}roteins.}, journal = {Cells}, volume = {12}, number = {4}, issn = {2073-4409}, address = {Basel}, publisher = {MDPI}, reportid = {DZNE-2023-00310}, pages = {569}, year = {2023}, note = {CC BY}, abstract = {Neuron-to-neuron transfer of pathogenic α-synuclein species is a mechanism of likely relevance to Parkinson's disease development. Experimentally, interneuronal α-synuclein spreading from the low brainstem toward higher brain regions can be reproduced by the administration of AAV vectors encoding for α-synuclein into the mouse vagus nerve. The aim of this study was to determine whether α-synuclein's spreading ability is shared by other proteins. Given α-synuclein synaptic localization, experiments involved intravagal injections of AAVs encoding for other synaptic proteins, β-synuclein, VAMP2, or SNAP25. Administration of AAV-VAMP2 or AAV-SNAP25 caused robust transduction of either of the proteins in the dorsal medulla oblongata but was not followed by interneuronal VAMP2 or SNAP25 transfer and caudo-rostral spreading. In contrast, AAV-mediated β-synuclein overexpression triggered its spreading to more frontal brain regions. The aggregate formation was investigated as a potential mechanism involved in protein spreading, and consistent with this hypothesis, results showed that overexpression of β-synuclein, but not VAMP2 or SNAP25, in the dorsal medulla oblongata was associated with pronounced protein aggregation. Data indicate that interneuronal protein transfer is not a mere consequence of increased expression or synaptic localization. It is rather promoted by structural/functional characteristics of synuclein proteins that likely include their tendency to form aggregate species.}, keywords = {Mice / Animals / alpha-Synuclein: metabolism / beta-Synuclein: metabolism / Parkinson Disease: metabolism / Brain: metabolism / Brain Stem: pathology / Vesicle-Associated Membrane Protein 2: metabolism / Parkinson’s disease (Other) / Parkinson’s disease (Other) / animal models (Other) / oligomerization (Other) / protein spreading (Other) / vagus nerve (Other) / alpha-Synuclein (NLM Chemicals) / beta-Synuclein (NLM Chemicals) / Vesicle-Associated Membrane Protein 2 (NLM Chemicals)}, cin = {AG Di Monte}, ddc = {570}, cid = {I:(DE-2719)1013008}, pnm = {352 - Disease Mechanisms (POF4-352)}, pid = {G:(DE-HGF)POF4-352}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:36831238}, pmc = {pmc:PMC9954582}, doi = {10.3390/cells12040569}, url = {https://pub.dzne.de/record/256448}, }