Proteolytic degradation patterns of the receptor for advanced glycation end products peptide fragments correlate with their neuroprotective activity in Alzheimer's disease models

The receptor for advanced glycation end products (RAGE) plays an essential role in Alzheimer's disease (AD). We previously demonstrated that a fragment (60–76) of RAGE improved the memory of olfactory bulbectomized (OBX) and Tg 5 × FAD mice – animal models of AD. The peptide analog (60–76) with...

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Bibliographic Details
Published in:Drug development research 2021-12, Vol.82 (8), p.1217-1226
Main Authors: Volpina, Olga M., Koroev, Dmitriy O., Serebryakova, Marina V., Volkova, Tatyana D., Kamynina, Anna V., Bobkova, Natalia V.
Format: Article
Language:English
Subjects:
Advanced glycosylation end products
Alzheimer Disease - drug therapy
Alzheimer's disease
Animal models
Animals
Chromatography, High Pressure Liquid
Disease Models, Animal
Fragments
Glycosylation
High-performance liquid chromatography
Liquid chromatography
Male
Mass Spectrometry
Mass spectroscopy
Memory tasks
Mental task performance
Mice
Neurodegenerative diseases
Neuroprotection
Neuroprotective Agents - therapeutic use
Peptide Fragments - therapeutic use
Peptides
Proteolysis
Receptor for Advanced Glycation End Products - metabolism
Receptors
Scientific imaging
Spatial analysis
Spatial memory
Spectroscopy
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Summary:The receptor for advanced glycation end products (RAGE) plays an essential role in Alzheimer's disease (AD). We previously demonstrated that a fragment (60–76) of RAGE improved the memory of olfactory bulbectomized (OBX) and Tg 5 × FAD mice – animal models of AD. The peptide analog (60–76) with protected N‐ and C‐terminal groups was more active than the free peptide in Tg 5 × FAD mice. This study investigated proteolytic cleavage of the RAGE fragment (60–76) and its C‐ and N‐terminally modified analog by blood serum using HPLC and mass spectrometry. The modified peptide was proteolyzed slower than the free peptide. Degrading the protected analog resulted in shortened fragments with memory‐enhancing effects, whereas the free peptide yielded inactive fragments. After administering the different peptides to OBX mice, their performance in a spatial memory task revealed that the effective dose of the modified peptide was five times lower than that of the free peptide. HPLC and mass spectrometry analysis of the proteolytic products allowed us to clarify the differences in the neuroprotective activity conferred by administering these two peptides to AD animal models. The current study suggests that the modified RAGE fragment is more promising for the development of anti‐AD therapy than its free analog.
ISSN:0272-4391
1098-2299
DOI:10.1002/ddr.21836