TY  - JOUR
AU  - Klinkenberg, Michael
AU  - Helwig, Michael
AU  - Pinto-Costa, Rita
AU  - Rollar, Angela
AU  - Rusconi, Raffaella
AU  - Di Monte, Donato A
AU  - Ulusoy, Ayse
TI  - Interneuronal In Vivo Transfer of Synaptic Proteins.
JO  - Cells
VL  - 12
IS  - 4
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DZNE-2023-00310
SP  - 569
PY  - 2023
N1  - CC BY
AB  - 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.
KW  - Mice
KW  - Animals
KW  - alpha-Synuclein: metabolism
KW  - beta-Synuclein: metabolism
KW  - Parkinson Disease: metabolism
KW  - Brain: metabolism
KW  - Brain Stem: pathology
KW  - Vesicle-Associated Membrane Protein 2: metabolism
KW  - Parkinson’s disease (Other)
KW  - Parkinson’s disease (Other)
KW  - animal models (Other)
KW  - oligomerization (Other)
KW  - protein spreading (Other)
KW  - vagus nerve (Other)
KW  - alpha-Synuclein (NLM Chemicals)
KW  - beta-Synuclein (NLM Chemicals)
KW  - Vesicle-Associated Membrane Protein 2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36831238
C2  - pmc:PMC9954582
DO  - DOI:10.3390/cells12040569
UR  - https://pub.dzne.de/record/256448
ER  -