In Vitro and In Vivo Efficacies of the Linear and the Cyclic Version of an All-d-Enantiomeric Peptide Developed for the Treatment of Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. The Cyclic d-Peptide cRD2D3 Revealed Increased In Vitro Potency Compared to the Linear d-Peptide RD2D3 Without Differences in the Proteolytic Stability
2.2. Tg-SwDI Mice Develop Cognitive Deficits at 12 Months of Age Compared to WT Mice
2.3. RD2D3 Showed Superior Efficacy to Improve Phenotypic Deficits over cRD2D3
3. Discussion
4. Materials and Methods
4.1. Peptides
4.2. In Vitro Potency
4.2.1. Binding Affinity
4.2.2. Thioflavin-T Assay
4.2.3. QIAD Assay
4.2.4. Proteolytic Stability
4.3. In Vivo Efficacy
4.3.1. Animals
4.3.2. Ethical Approval
4.3.3. Characterization
4.3.4. Nesting Behavior
4.3.5. Marble Burying
4.3.6. Open Field Test
4.3.7. Morris Water Maze
4.4. Treatment
4.5. Histology
4.6. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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6E10 IR (%) | GFAP IR (%) | Iba-1 IR (%) | ||||
---|---|---|---|---|---|---|
Cortex | Hippocampus | Cortex | Hippocampus | Cortex | Hippocampus | |
Placebo | 1.8 ± 0.7 | 2.5 ± 0.7 | 43.8 ± 2.0 | 39.8 ± 1.0 | 8.7 ± 1.7 | 11. 5 ± 1.1 |
RD2D3 | 1.0 ± 0.2 | 2.5 ± 0.5 | 40.6 ± 2.2 | 38.0 ± 1.2 | 8.1 ± 1.6 | 8.6 ± 1.3 |
cRD2D3 | 1.1 ± 0.2 | 4.2 ± 0.7 | 43.1 ± 1.8 | 39.5 ± 1.0 | 8.1 ± 1.6 | 10.2 ± 1.8 |
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Schemmert, S.; Camargo, L.C.; Honold, D.; Gering, I.; Kutzsche, J.; Willuweit, A.; Willbold, D. In Vitro and In Vivo Efficacies of the Linear and the Cyclic Version of an All-d-Enantiomeric Peptide Developed for the Treatment of Alzheimer’s Disease. Int. J. Mol. Sci. 2021, 22, 6553. https://doi.org/10.3390/ijms22126553
Schemmert S, Camargo LC, Honold D, Gering I, Kutzsche J, Willuweit A, Willbold D. In Vitro and In Vivo Efficacies of the Linear and the Cyclic Version of an All-d-Enantiomeric Peptide Developed for the Treatment of Alzheimer’s Disease. International Journal of Molecular Sciences. 2021; 22(12):6553. https://doi.org/10.3390/ijms22126553
Chicago/Turabian StyleSchemmert, Sarah, Luana Cristina Camargo, Dominik Honold, Ian Gering, Janine Kutzsche, Antje Willuweit, and Dieter Willbold. 2021. "In Vitro and In Vivo Efficacies of the Linear and the Cyclic Version of an All-d-Enantiomeric Peptide Developed for the Treatment of Alzheimer’s Disease" International Journal of Molecular Sciences 22, no. 12: 6553. https://doi.org/10.3390/ijms22126553
APA StyleSchemmert, S., Camargo, L. C., Honold, D., Gering, I., Kutzsche, J., Willuweit, A., & Willbold, D. (2021). In Vitro and In Vivo Efficacies of the Linear and the Cyclic Version of an All-d-Enantiomeric Peptide Developed for the Treatment of Alzheimer’s Disease. International Journal of Molecular Sciences, 22(12), 6553. https://doi.org/10.3390/ijms22126553