Effects of the Pentapeptide P33 on Memory and Synaptic Plasticity in APP/PS1 Transgenic Mice: A Novel Mechanism Presenting the Protein Fe65 as a Target
Abstract
:1. Introduction
2. Results
2.1. P33 Binds to Fe65-WW but Not to Pin1-WW In Vitro
2.2. P33 Treatment Does Not Influence Key Protein Levels Involved in the Fe65/APP Route in the Transgenic Mice
2.3. P33 Restores the Pathologically Reduced Spine Density and Protects the Synapses
2.4. P33 Significantly Reduces the Amounts of Both Soluble and Deposited Aβ Forms in the APP/PS1 Animals
2.5. P33 Hinders Inflammatory Processes in the Mouse Brain
2.6. P33 Exerts a Positive Effect on the Learning Ability and Memory Functions in an MWM Paradigm
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Synthesis
4.3. Purification
4.4. ITC
4.5. Animals
4.6. MWM
4.7. ELISA
4.8. WB
4.9. Quantification of Spine Density
4.10. Immunohistochemistry
4.11. Quantification of the Immunohistochemical Data
4.12. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
RIP | regulated intramembrane proteolysis |
APP | amyloid precursor protein |
AICD | intracellular domain of APP |
AD | Alzheimer’s disease |
Aβ | beta amyloid |
HEK293 | human embryonic kidney cells 293 |
H4 | human H4 neuroglioma cells |
MDCK | Madin–Darby Canine Kidney cells |
ITC | isothermal titration calorimetry |
APP/PS1 | APPswe/PS1ΔE9 double transgenic |
WT | C57BL/6 wild type |
MWM | Morris water maze |
GFAP | glial fibrillary acidic protein |
Iba1 | ionized calcium-binding adapter molecule 1 |
DCC | N,N′-dicyclohexyl-carbodiimide |
HOBt | 1-hydroxybenzotriazole |
HATU | 1-[bis(dimethylamino)-methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxid hexafluorophos-phate |
MBHA x HCl | 4-methylbenz-hydryl-amine hydrochloride |
DIPEA | N,N-diisopropylethylamine |
TFA | trifluoroacetic acid |
ACN | acetonitrile |
RT | room temperature |
HC | hippocampus |
CTX | cerebral cortex |
WB | Western blot |
TBS | Tris-buffered saline |
BSA | bovine serum albumin |
DAB | 3,3′-diaminobenzidine |
DPX | dibutyl phthalate xylene |
ROI | regions of interest |
CNS | central nervous system |
mFe65 | mouse Fe65 |
hAPP | human APP |
ELISA | enzyme-linked immunosorbent assay |
PSD95 | postsynaptic density protein 95 |
SYN | synaptophysin |
NFT | neurofibrillary tangles |
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Szögi, T.; Schuster, I.; Borbély, E.; Gyebrovszki, A.; Bozsó, Z.; Gera, J.; Rajkó, R.; Sántha, M.; Penke, B.; Fülöp, L. Effects of the Pentapeptide P33 on Memory and Synaptic Plasticity in APP/PS1 Transgenic Mice: A Novel Mechanism Presenting the Protein Fe65 as a Target. Int. J. Mol. Sci. 2019, 20, 3050. https://doi.org/10.3390/ijms20123050
Szögi T, Schuster I, Borbély E, Gyebrovszki A, Bozsó Z, Gera J, Rajkó R, Sántha M, Penke B, Fülöp L. Effects of the Pentapeptide P33 on Memory and Synaptic Plasticity in APP/PS1 Transgenic Mice: A Novel Mechanism Presenting the Protein Fe65 as a Target. International Journal of Molecular Sciences. 2019; 20(12):3050. https://doi.org/10.3390/ijms20123050
Chicago/Turabian StyleSzögi, Titanilla, Ildikó Schuster, Emőke Borbély, Andrea Gyebrovszki, Zsolt Bozsó, János Gera, Róbert Rajkó, Miklós Sántha, Botond Penke, and Lívia Fülöp. 2019. "Effects of the Pentapeptide P33 on Memory and Synaptic Plasticity in APP/PS1 Transgenic Mice: A Novel Mechanism Presenting the Protein Fe65 as a Target" International Journal of Molecular Sciences 20, no. 12: 3050. https://doi.org/10.3390/ijms20123050