Proteolytic degradation patterns of the receptor for advanced glycation end products peptide fragments correlate with their neuroprotective activity in Alzheimer's disease models
| Autor: | T. D. Volkova, D. O. Koroev, Natalia V. Bobkova, Marina V. Serebryakova, A. V. Kamynina, Olga M. Volpina |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Proteolysis Receptor for Advanced Glycation End Products Peptide Neuroprotection Mass Spectrometry RAGE (receptor) 03 medical and health sciences Mice 0302 clinical medicine Blood serum Glycation Alzheimer Disease Drug Discovery medicine Animals Receptor Chromatography High Pressure Liquid chemistry.chemical_classification Peptide analog medicine.diagnostic_test Chemistry Peptide Fragments Disease Models Animal Neuroprotective Agents Biochemistry 030220 oncology & carcinogenesis 030217 neurology & neurosurgery |
| Zdroj: | Drug development researchREFERENCES. 82(8) |
| ISSN: | 1098-2299 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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