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Role of RAGE in Alzheimer’s Disease

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Abstract

Receptor for advanced glycation end products (RAGE) is a receptor of the immunoglobulin super family that plays various important roles under physiological and pathological conditions. Compelling evidence suggests that RAGE acts as both an inflammatory intermediary and a critical inducer of oxidative stress, underlying RAGE-induced Alzheimer-like pathophysiological changes that drive the process of Alzheimer’s disease (AD). A critical role of RAGE in AD includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles, failure of synaptic transmission, and neuronal degeneration. The steady-state level of Aβ depends on the balance between production and clearance. RAGE plays an important role in the Aβ clearance. RAGE acts as an important transporter via regulating influx of circulating Aβ into brain, whereas the efflux of brain-derived Aβ into the circulation via BBB is implemented by LRP1. RAGE could be an important contributor to Aβ generation via enhancing the activity of β- and/or γ-secretases and activating inflammatory response and oxidative stress. However, sRAGE–Aβ interactions could inhibit Aβ neurotoxicity and promote Aβ clearance from brain. Meanwhile, RAGE could be a promoting factor for the synaptic dysfunction and neuronal circuit dysfunction which are both the material structure of cognition, and the physiological and pathological basis of cognition. In addition, RAGE could be a trigger for the pathogenesis of Aβ and tau hyper-phosphorylation which both participate in the process of cognitive impairment. Preclinical and clinical studies have supported that RAGE inhibitors could be useful in the treatment of AD. Thus, an effective measure to inhibit RAGE may be a novel drug target in AD.

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Acknowledgments

This work was supported by the Hubei Province Health and Family Planning Scientific Research Project (WJ2015MB219), the Hubei Provincial Nature Science Foundation (2105CFB260) and the Nature Science Foundation of Shiyan Renmin Hospital to Dr. Zhiyou Cai.

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Authors and Affiliations

  1. Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, No. 39 Chaoyang Middle Road, Shiyan, 442000, Hubei Province, People’s Republic of China

    Zhiyou Cai, Nannuan Liu, Chuanling Wang & Biyong Qin

  2. Physical Examination Center, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, 442000, Hubei Province, People’s Republic of China

    Yingjun Zhou

  3. Department of Anatomy, Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China

    Ming Xiao

  4. Department of Neurology, Xiangyang Center Hospital, The First Affiliated Hospital, Hubei University of Arts and Science, Xiangyang, 441021, Hubei Province, People’s Republic of China

    Liying Chang

  5. Department of Pharmaceutical Sciences,UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA

    Liang-Jun Yan

  6. Department of Neurology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, Guangdong Province, People’s Republic of China

    Bin Zhao

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  1. Zhiyou Cai
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Correspondence to Zhiyou Cai.

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Cai, Z., Liu, N., Wang, C. et al. Role of RAGE in Alzheimer’s Disease. Cell Mol Neurobiol 36, 483–495 (2016). https://doi.org/10.1007/s10571-015-0233-3

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