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

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Abstract

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

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Acknowledgments

This work was support by the CRI Grant (NRF-2013R1A2A1A01016896) and the Open Research Program (KIST to YKJ, 2E24582-14-071) funded by the Ministry of Education, Science and Technology.

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The authors declare that they have no conflict of interest.

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  1. Global Research Laboratory, School of Biological Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-747, Korea

    Tae-In Kam, Youngdae Gwon & Yong-Keun Jung

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Kam, TI., Gwon, Y. & Jung, YK. Amyloid beta receptors responsible for neurotoxicity and cellular defects in Alzheimer’s disease. Cell. Mol. Life Sci. 71, 4803–4813 (2014). https://doi.org/10.1007/s00018-014-1706-0

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