Interaction between Angiotensin Receptor and β-Adrenergic Receptor Regulates the Production of Amyloid β-Protein.

Interaction between Angiotensin Receptor and β-Adrenergic Receptor Regulates the Production of Amyloid β-Protein. Biol Pharm Bull. 2020;43(4):731-735 Authors: Kikuchi K, Fujita Y, Shen X, Liu J, Terakawa T, Nishikata D, Niibori S, Ito T, Ashidate K, Kikuchi T, Kikuchi Y, Maeda T, Zou K, Komano H Abstract Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid β-protein (Aβ) within the parenchyma of the brain. Aβ is considered to be the key pathogenic factor of AD. Recently, we showed that Angiotensin II type 1 receptor (AT1R), which regulates blood pressure, is involved in Aβ production, and that telmisartan (Telm), which is an angiotensin II receptor blocker (ARB), increased Aβ production via AT1R. However, the precise mechanism underlying how AT1R is involved in Aβ production is unknown. Interestingly, AT1R, a G protein-coupled receptor, was strongly suggested to be involved in signal transduction by heterodimerization with β2-adrenergic receptor (β2-AR), which is also shown to be involved in Aβ generation. Therefore, in this study, we aimed to clarify whether the interaction between AT1R and β2-AR is involved in the regulation of Aβ production. To address this, we analyzed whether the increase in Aβ production by Telm treatment is affected by β-AR antagonist using fibroblasts overexpressing amyloid precursor protein (APP). We found that the increase in Aβ p...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research