The Small Molecule Alpha-Synuclein Aggregator, FN075, Enhances Alpha-Synuclein Pathology in Subclinical AAV Rat Models
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals & Ethical Statement
2.2. Experimental Design
2.3. AAV Virus Production
2.4. Surgery
2.5. Behavioral Testing
2.6. Euthanasia and Tissue Processing
2.7. Immunohistochemistry
2.8. Image Analysis
2.9. Statistical Analysis
3. Results
3.1. AAV-α-Synuclein Administration Induced Significant Alpha-Synuclein Expression
3.2. FN075 Significantly Increased Phosphorylation of Alpha-Synuclein at Serine 129
3.3. FN075 Did Not Precipitate Neurodegeneration in the Nigrostriatal Pathway in Preclinical AAV Models
3.4. FN075 Did Not Precipitate Motor Impairment in the Nigrostriatal Pathway in Preclinical AAV Models
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study 1: Wild-Type Experiment | |||
Group | Virus injection | FN075 injection | n |
Control | AAV-GFP | Vehicle | 10 |
FN075 | AAV-GFP | FN075 | 10 |
AAV-α-SYN (WT) | AAV-α-synuclein (wild-type) | Vehicle | 10 |
AAV-α-SYN (WT) & FN075 | AAV-α-synuclein (wild-type) | FN075 | 10 |
Study 2: A53T Mutant Experiment | |||
Group | Virus injection | FN075 injection | n |
Control | AAV-GFP | Vehicle | 9 |
FN075 | AAV-GFP | FN075 | 8 |
AAV-α-SYN (A53T) | AAV-α-synuclein (A53T mutant) | Vehicle | 9 |
AAV-α-SYN (A53T) & FN075 | AAV-α-synuclein (A53T mutant) | FN075 | 10 |
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Kelly, R.; Cairns, A.G.; Ådén, J.; Almqvist, F.; Bemelmans, A.-P.; Brouillet, E.; Patton, T.; McKernan, D.P.; Dowd, E. The Small Molecule Alpha-Synuclein Aggregator, FN075, Enhances Alpha-Synuclein Pathology in Subclinical AAV Rat Models. Biomolecules 2021, 11, 1685. https://doi.org/10.3390/biom11111685
Kelly R, Cairns AG, Ådén J, Almqvist F, Bemelmans A-P, Brouillet E, Patton T, McKernan DP, Dowd E. The Small Molecule Alpha-Synuclein Aggregator, FN075, Enhances Alpha-Synuclein Pathology in Subclinical AAV Rat Models. Biomolecules. 2021; 11(11):1685. https://doi.org/10.3390/biom11111685
Chicago/Turabian StyleKelly, Rachel, Andrew G. Cairns, Jörgen Ådén, Fredrik Almqvist, Alexis-Pierre Bemelmans, Emmanuel Brouillet, Tommy Patton, Declan P. McKernan, and Eilís Dowd. 2021. "The Small Molecule Alpha-Synuclein Aggregator, FN075, Enhances Alpha-Synuclein Pathology in Subclinical AAV Rat Models" Biomolecules 11, no. 11: 1685. https://doi.org/10.3390/biom11111685