000256448 001__ 256448 000256448 005__ 20240403131748.0 000256448 0247_ $$2doi$$a10.3390/cells12040569 000256448 0247_ $$2pmid$$apmid:36831238 000256448 0247_ $$2pmc$$apmc:PMC9954582 000256448 0247_ $$2altmetric$$aaltmetric:142978988 000256448 037__ $$aDZNE-2023-00310 000256448 041__ $$aEnglish 000256448 082__ $$a570 000256448 1001_ $$0P:(DE-2719)2810845$$aKlinkenberg, Michael$$b0$$eFirst author 000256448 245__ $$aInterneuronal In Vivo Transfer of Synaptic Proteins. 000256448 260__ $$aBasel$$bMDPI$$c2023 000256448 3367_ $$2DRIVER$$aarticle 000256448 3367_ $$2DataCite$$aOutput Types/Journal article 000256448 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1711373188_22709 000256448 3367_ $$2BibTeX$$aARTICLE 000256448 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000256448 3367_ $$00$$2EndNote$$aJournal Article 000256448 500__ $$aCC BY 000256448 520__ $$aNeuron-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. 000256448 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000256448 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000256448 650_7 $$2Other$$aParkinson’s disease 000256448 650_7 $$2Other$$aParkinson’s disease 000256448 650_7 $$2Other$$aanimal models 000256448 650_7 $$2Other$$aoligomerization 000256448 650_7 $$2Other$$aprotein spreading 000256448 650_7 $$2Other$$avagus nerve 000256448 650_7 $$2NLM Chemicals$$aalpha-Synuclein 000256448 650_7 $$2NLM Chemicals$$abeta-Synuclein 000256448 650_7 $$2NLM Chemicals$$aVesicle-Associated Membrane Protein 2 000256448 650_2 $$2MeSH$$aMice 000256448 650_2 $$2MeSH$$aAnimals 000256448 650_2 $$2MeSH$$aalpha-Synuclein: metabolism 000256448 650_2 $$2MeSH$$abeta-Synuclein: metabolism 000256448 650_2 $$2MeSH$$aParkinson Disease: metabolism 000256448 650_2 $$2MeSH$$aBrain: metabolism 000256448 650_2 $$2MeSH$$aBrain Stem: pathology 000256448 650_2 $$2MeSH$$aVesicle-Associated Membrane Protein 2: metabolism 000256448 7001_ $$0P:(DE-2719)2810665$$aHelwig, Michael$$b1$$udzne 000256448 7001_ $$0P:(DE-2719)9001609$$aPinto-Costa, Rita$$b2$$udzne 000256448 7001_ $$0P:(DE-2719)2812656$$aRollar, Angela$$b3$$udzne 000256448 7001_ $$0P:(DE-2719)2810495$$aRusconi, Raffaella$$b4$$udzne 000256448 7001_ $$0P:(DE-2719)2481741$$aDi Monte, Donato A$$b5$$udzne 000256448 7001_ $$0P:(DE-2719)2772760$$aUlusoy, Ayse$$b6$$eLast author$$udzne 000256448 770__ $$aAlpha-Synuclein Pathology in Human Diseases 000256448 773__ $$0PERI:(DE-600)2661518-6$$a10.3390/cells12040569$$gVol. 12, no. 4, p. 569 -$$n4$$p569$$tCells$$v12$$x2073-4409$$y2023 000256448 8564_ $$uhttps://pub.dzne.de/record/256448/files/DZNE-2023-00310.pdf$$yOpenAccess 000256448 8564_ $$uhttps://pub.dzne.de/record/256448/files/DZNE-2023-00310.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 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