Version 1
: Received: 2 May 2024 / Approved: 3 May 2024 / Online: 3 May 2024 (07:51:06 CEST)
How to cite:
Höfs, L.; Geissler-Lösch, D.; Wunderlich, K.; Szegö, E. M.; van den Haute, C.; Baekelandt, V.; Hoyer, W.; Falkenburger, B. H. Evaluation of the Effect of β-Wrapin AS69 in a Mouse Model Based on Alpha-Synuclein Overexpression. Preprints2024, 2024050175. https://doi.org/10.20944/preprints202405.0175.v1
Höfs, L.; Geissler-Lösch, D.; Wunderlich, K.; Szegö, E. M.; van den Haute, C.; Baekelandt, V.; Hoyer, W.; Falkenburger, B. H. Evaluation of the Effect of β-Wrapin AS69 in a Mouse Model Based on Alpha-Synuclein Overexpression. Preprints 2024, 2024050175. https://doi.org/10.20944/preprints202405.0175.v1
Höfs, L.; Geissler-Lösch, D.; Wunderlich, K.; Szegö, E. M.; van den Haute, C.; Baekelandt, V.; Hoyer, W.; Falkenburger, B. H. Evaluation of the Effect of β-Wrapin AS69 in a Mouse Model Based on Alpha-Synuclein Overexpression. Preprints2024, 2024050175. https://doi.org/10.20944/preprints202405.0175.v1
APA Style
Höfs, L., Geissler-Lösch, D., Wunderlich, K., Szegö, E. M., van den Haute, C., Baekelandt, V., Hoyer, W., & Falkenburger, B. H. (2024). Evaluation of the Effect of β-Wrapin AS69 in a Mouse Model Based on Alpha-Synuclein Overexpression. Preprints. https://doi.org/10.20944/preprints202405.0175.v1
Chicago/Turabian Style
Höfs, L., Wolfgang Hoyer and Björn H Falkenburger. 2024 "Evaluation of the Effect of β-Wrapin AS69 in a Mouse Model Based on Alpha-Synuclein Overexpression" Preprints. https://doi.org/10.20944/preprints202405.0175.v1
Abstract
Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFF). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence stainings were used as outcomes.Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
