TY - JOUR
T1 - Role of RAGE in Alzheimer’s Disease
AU - Cai, Zhiyou
AU - Liu, Nannuan
AU - Wang, Chuanling
AU - Qin, Biyong
AU - Zhou, Yingjun
AU - Xiao, Ming
AU - Chang, Liying
AU - Yan, Liang Jun
AU - Zhao, Bin
N1 - Funding Information:
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.
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Beta-amyloid
KW - Cognitive impairment
KW - Receptor for advanced glycation end products
KW - Tau hyperphosphorylation
UR - http://www.scopus.com/inward/record.url?scp=84969497763&partnerID=8YFLogxK
U2 - 10.1007/s10571-015-0233-3
DO - 10.1007/s10571-015-0233-3
M3 - Review article
C2 - 26175217
AN - SCOPUS:84969497763
SN - 0272-4340
VL - 36
SP - 483
EP - 495
JO - Cellular and Molecular Neurobiology
JF - Cellular and Molecular Neurobiology
IS - 4
ER -