Synthetic Fragments of Receptor for Advanced Glycation End Products Bind Beta-Amyloid 1–40 and Protect Primary Brain Cells From Beta-Amyloid Toxicity

Abstract

Receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of Alzheimer’s disease. We have previously revealed that RAGE fragment sequence (60–76) and its shortened analogs sequence (60–70) and (60–65) under intranasal insertion were able to restore memory and improve morphological and biochemical state of neurons in the brain of bulbectomized mice developing major AD features. In the current study, we have investigated the ability of RAGE peptide (60–76) and five shortened analogs to bind beta-amyloid (Aβ) 1–40 in an fluorescent titration test and show that all the RAGE fragments apart from one [sequence (65–76)] were able to bind Aβ in vitro. Moreover, we show that all RAGE fragments apart from the shortest one (60–62), were able to protect neuronal primary cultures from amyloid toxicity, by preventing the caspase 3 activation induced by Aβ 1–42. We have compared the data obtained in the present research with the previously published data in the animal model of AD, and offer a probable mechanism of neuroprotection of the RAGE peptide.

Pathological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: the Receptor for Advanced Glycation End Products (RAGE)

“…Lysine or arginine residues of proteins and glucose, moving towards the Schiff-base, convert themselves to the more stable aminomethyl ketone by the Amadori rearrangement and finally result in the formation of advanced glycation end (AGE) products (Bunn and Higgins, 1981 ; Hartog et al, 2007 ; Rabbani and Ahn, 2019 ). The synthesis of AGEs is irreversible, and although the process of cell death is slow and insignificant, the non-enzymatic saccharification process accompanied by neuron metabolism seriously affects the normal functioning of the nervous system (Kamynina et al, 2018 ). Therefore, AGEs and the receptor for advanced glycation end-products (RAGE) may play an important role in disease pathogenesis.…”

The Neuroprotective Effect of L-Carnitine against Glyceraldehyde-Induced Metabolic Impairment: Possible Implications in Alzheimer’s Disease

“…Primary rat cortical neurons were prepared from the cortex of Wistar rat pups (P2-P4) (Charles River, Lecco, Italy) as previously described [15,37]. The experimental procedures were performed in full compliance with the Committee for Animal Welfare of the University "Politecnica delle Marche" (project 40A31N.G22) and in strict accordance with the guidelines of the Italian Ministry of Health (D.L.…”

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

“…We co‐cultured primary neurons and astrocytes from the hippocampus and cortex of rat brains, treated them with peptide (60–76), and observed a reduction in Aβ 1–42 toxicity compared to that without treatment. Additionally, the (60–76) peptide binds Aβ 1–40 in vitro (Kamynina et al, 2018).…”