title: Role of RAGE in Alzheimer's Disease.
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.
authors.affiliation: 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. c0909@hotmail.com.
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Nannuan
authors.initials: N
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Chuanling
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Biyong
authors.initials: B
authors.lastname: Qin
authors.affiliation: Physical Examination Center, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, 442000, Hubei Province, People's Republic of China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anatomy, Nanjing Medical University, Nanjing, 210029, Jiangsu, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Liying
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Pharmaceutical Sciences,UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA.
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Yan
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, Guangdong Province, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*
chemical_list: D000682:Amyloid; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products
keywords: Alzheimer’s disease; Beta-amyloid; Cognitive impairment; Receptor for advanced glycation end products; Tau hyperphosphorylation