%0 Journal Article
%A Klinkenberg, Michael
%A Helwig, Michael
%A Pinto-Costa, Rita
%A Rollar, Angela
%A Rusconi, Raffaella
%A Di Monte, Donato A
%A Ulusoy, Ayse
%T Interneuronal In Vivo Transfer of Synaptic Proteins.
%J Cells
%V 12
%N 4
%@ 2073-4409
%C Basel
%I MDPI
%M DZNE-2023-00310
%P 569
%D 2023
%Z CC BY
%X 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.
%K Mice
%K Animals
%K alpha-Synuclein: metabolism
%K beta-Synuclein: metabolism
%K Parkinson Disease: metabolism
%K Brain: metabolism
%K Brain Stem: pathology
%K Vesicle-Associated Membrane Protein 2: metabolism
%K Parkinson’s disease (Other)
%K Parkinson’s disease (Other)
%K animal models (Other)
%K oligomerization (Other)
%K protein spreading (Other)
%K vagus nerve (Other)
%K alpha-Synuclein (NLM Chemicals)
%K beta-Synuclein (NLM Chemicals)
%K Vesicle-Associated Membrane Protein 2 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36831238
%2 pmc:PMC9954582
%R 10.3390/cells12040569
%U https://pub.dzne.de/record/256448