Endogenous secretory receptor for advanced glycation end-products inhibits amyloid-β1-42 uptake into mouse brain.

Abstract

The cell-surface receptor for advanced glycation end-products (RAGE) has been implicated in the development of diabetic vascular complications and Alzheimer's disease. RAGE has been considered to be involved in amyloid-β1-42 (Aβ1-42) uptake into brain. In the present study, we demonstrate that endogenous secretory RAGE (esRAGE), a decoy form of RAGE generated by alternative RNA processing, is able to inhibit Aβ1-42 influx into mouse brain. Surface plasmon resonance and competitive binding assays revealed that human Aβ1-42 interacted with human esRAGE within the immunoglobulin V type region. We next examined the uptake and distribution of 125I-labeled human Aβ1-42 in various organs and body fluids of newly created mice overexpressing human esRAGE as well as RAGE-null and wild-type (WT) mice. The transition of the 125I-labeled Aβ1-42 from circulation to brain parenchyma peaked at 30 min after the injection into WT mice, but this was significantly blunted in esRAGE-overexpressing and RAGE-null mice. Significant reduction in 125I-labeled Aβ1-42-derived photo-stimulated luminescence were marked in ventricles, cerebral cortex, hippocampus, especially CA1 and CA3 regions, putamen, and thalamus. The results thus suggest the potential of esRAGE in protection against the development of Alzheimer's disease.

• Authors: Takahiro Sugihara, Seiichi Munesue, Yasuhiko Yamamoto, Shigeru Sakurai, Nasima Akhter, Yoji Kitamura, Kazuhiro Shiba, Takuo Watanabe, Hideto Yonekura, Yasuhiko Hayashi, Jun-Ichiro Hamada, Hiroshi Yamamoto
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 28 Issue 3 Pg. 709-20 ( 2012) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 22064071 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Iodine Isotopes
• Peptide Fragments
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• amyloid beta-protein (1-42)

Topics

• Amyloid beta-Peptides (metabolism)
• Animals
• Autoradiography
• Brain (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Humans
• Iodine Isotopes (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Peptide Fragments (metabolism)
• Protein Binding (genetics)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (genetics, metabolism)
• Surface Plasmon Resonance
• Time Factors
• Tissue Distribution (genetics)