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 protected N- and C-terminal groups was more active than the free peptide in Tg 5 × FAD mice.

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

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 .

Synthetic Fragment of Receptor for Advanced Glycation End Products Prevents Memory Loss and Protects Brain Neurons in Olfactory Bulbectomized Mice.

Activation of receptor for advanced glycation end products (RAGE) plays an essential role in the development of Alzheimer's disease (AD). It is known that the soluble isoform of the receptor binds to ligands and prevents negative effects of the receptor activation. We proposed that peptide fragments from RAGE prevent negative effects of the receptor activation during AD neurodegeneration.

Acetylcholine and antibodies against the acetylcholine receptor protect neurons and astrocytes against beta-amyloid toxicity.

Aggregated amyloid-β causes pathological changes in mixed cultures of neurons and astrocytes such as sporadic cytoplasmic intracellular Ca(2+)-signalling, increase in reactive oxygen species production and cell death. Some of the toxic effects of amyloid-β are mediated through the interaction of the peptide with α7-type nicotinic acetylcholine receptors at the cell surface. Here we demonstrated that affinity purified antibodies to synthetic fragment 173-193 of the α7-subunit of the nAChR are able to protect cells from amyloid-β induced cell death.

Vaccination with peptide 173-193 of acetylcholine receptor α7-subunit prevents memory loss in olfactory bulbectomized mice.

We studied the ability of four non-conjugated alpha7-subunit fragments of the nicotinic acetylcholine receptor to induce an immune response and to protect memory in olfactory bulbectomized mice which demonstrate abnormalities similar to Alzheimer's disease (AD). Vaccination only with the alpha7-subunit fragment 173-193 was shown to rescue spatial memory, to restore the level of alpha7 acetylcholine receptors in the cortex, and to prevent an increase in the amyloid-beta (Abeta) level in brain tissue in these animals. Antibodies against the peptide 173-193 were revealed in blood serum and cerebrospinal liquid in the bulbectomized mice.