Imperial College London
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ProfessorMagdalenaSastre

Faculty of Medicine, Department of Brain Sciences

Professor in Molecular Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 6673m.sastre

 
 
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Location

 

406Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mota:2022:10.3390/ijms23137320,
author = {Mota, B and Ashburner, N and Abelleira, L and Liu, L and Aleksynas, R and Rovati, LC and Caselli, G and Sastre, M},
doi = {10.3390/ijms23137320},
journal = {International Journal of Molecular Sciences},
title = {I2-imidazoline ligand CR4056 improves memory, increases ApoE expression and reduces BBB leakage in 5XFAD mice},
url = {http://dx.doi.org/10.3390/ijms23137320},
volume = {23},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer’s disease (AD). We recently demonstrated that the I2-ligand BU224 reversed memory impairments in AD transgenic mice and this effect was not consequence of reductions in Amyloid-β (Aβ) deposition. In this study, our aim was to determine the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD, since this ligand has been proven to be safely tolerated in humans. Sub-chronic oral administration of CR4056 (30 mg/kg for 10 days) led to an improvement in recognition memory in 6 months old 5xFAD mice, but not in wild-type littermates, without affecting Aβ levels or deposition.  Our results also revealed a change in the profile of microglia by CR4056, resulting in a suppression of pro-inflammatory activated microglia, but increased the density of astrocytes and the expression of ApoE, which is mainly produced by these glial cells. In addition, CR4056 restored fibrinogen extravasation, affecting the distribution of markers of astrocytic end feet in blood vessels. Therefore, these results suggest that CR4056 protects against Aβ-mediated neuroinflammation and vascular damage, and offers therapeutic potential at any stage of AD.
AU  - Mota,B
AU  - Ashburner,N
AU  - Abelleira,L
AU  - Liu,L
AU  - Aleksynas,R
AU  - Rovati,LC
AU  - Caselli,G
AU  - Sastre,M
DO  - 10.3390/ijms23137320
PY  - 2022///
SN  - 1422-0067
TI  - I2-imidazoline ligand CR4056 improves memory, increases ApoE expression and reduces BBB leakage in 5XFAD mice
T2  - International Journal of Molecular Sciences
UR  - http://dx.doi.org/10.3390/ijms23137320
UR  - https://www.mdpi.com/1422-0067/23/13/7320
UR  - http://hdl.handle.net/10044/1/97964
VL  - 23
ER  -
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