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• W3048144743 endingPage "104799" @default.
• W3048144743 startingPage "104799" @default.
• W3048144743 abstract "The receptor for advanced glycation end products (RAGE) is considered to contribute to the pathogenesis of Alzheimer's disease (AD), mediating amyloid beta (Aβ) accumulation, mitochondrial damage, and neuroinflammation. Previously, we have synthesized small peptides corresponding to the fragments (60–76) (P1) and (60–62) (P2) of the RAGE extracellular domain, and have shown that administration of P1 fragment but not P2 results in restoration of the spatial memory and decreases the brain Aβ (1–40) level in olfactory bulbectomized (OBX) mice demonstrating main features of Alzheimer's type neurodegeneration. In the present study, we have investigated the supposed mechanism of the therapeutic efficacy of P1 RAGE fragment and compared it to P2 short fragment. We have found that P1 restored activities of the respiratory chain in the Complexes I and IV in both cortical and hippocampal mitochondria of the OBX mice while P2 had no effect. Besides, fluorescein-labeled analog Flu-P1 bound to Aβ (1–40) and Aβ (1–42) with high affinity (Kd in the nanomolar range) whereas Flu-P2 revealed low affinity with tenfold higher Kd value for Aβ (1–40) and did not bind to Aβ (1–42). However, neither of the peptides had a notable impact on inflammation, estimated as mRNA expression of proinflammatory cytokines in the brain tissues of OBX mice. Taken together, our results suggest that direct Aβ-P1 interaction is one of the molecular events mediating the protection of the mitochondria in OBX animals from Aβ toxic effect. The RAGE fragment P1 would be the soluble decoy for Aβs and serve as a promising therapeutic agent against neurodegeneration accompanied by mitochondrial dysfunction." @default.
• W3048144743 created "2020-08-13" @default.
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• W3048144743 date "2020-11-01" @default.
• W3048144743 modified "2023-10-14" @default.
• W3048144743 title "Synthetic fragment (60–76) of RAGE improves brain mitochondria function in olfactory bulbectomized mice" @default.
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• W3048144743 doi "https://doi.org/10.1016/j.neuint.2020.104799" @default.
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