Amyloid beta receptors responsible for neurotoxicity and cellular defects in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease. Although a major cause of AD is the accumulation of amyloid-beta (A beta) peptide that induces neuronal loss and cognitive impairments, our understanding of its neurotoxic mechanisms is limited. Recent studies have identified putative A beta-binding receptors that mediate A beta neurotoxicity in cells and models of AD. Once A beta interacts with a receptor, a toxic signal is transduced into neurons, resulting in cellular defects including endoplasmic reticulum stress and mitochondrial dysfunction. In addition, A beta can also be internalized into neurons through unidentified A beta receptors and induces malfunction of subcellular organelles, which explains some part of A beta neurotoxicity. Understanding the neurotoxic signaling initiated by A beta-receptor binding and cellular defects provide insight into new therapeutic windows for AD. In the present review, we summarize the findings on A beta-binding receptors and the neurotoxicity of oligomeric A beta.