TY - JOUR
T1 - Toxic advanced glycation end products (TAGE) theory in Alzheimer's disease
AU - Sato, Takashi
AU - Shimogaito, Noriko
AU - Wu, Xuegang
AU - Kikuchi, Seiji
AU - Yamagishi, Sho Ichi
AU - Takeuchi, Masayoshi
PY - 2006
Y1 - 2006
N2 - Several epidemiological studies have reported moderately increased risks of Alzheimer's disease (AD) in diabetic patients compared with general population. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress more rapidly. Recent understanding of this process has confirmed that interactions between AGEs and their receptor (RAGE) may play a role in the pathogenesis of diabetic complications and AD. The authors have recently found that glyceraldehyde-derived AGEs (AGE-2), which is predominantly the structure of toxic AGEs (TAGE), show significant toxicity on cortical neuronal cells and that the neurotoxic effect of diabetic serum is completely blocked by neutralizing antibody against the AGE-2 epitope. Moreover, in human AD brains, AGE-2 is distributed in the cytosol of neurons in the hippocampus and parahippocampal gyrus. These results suggest that TAGE is involved in the pathogenesis of AD as well as other age-related diseases. In this review, the authors discuss the molecular mechanisms of AD, especially focusing on TAGE-RAGE system.
AB - Several epidemiological studies have reported moderately increased risks of Alzheimer's disease (AD) in diabetic patients compared with general population. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress more rapidly. Recent understanding of this process has confirmed that interactions between AGEs and their receptor (RAGE) may play a role in the pathogenesis of diabetic complications and AD. The authors have recently found that glyceraldehyde-derived AGEs (AGE-2), which is predominantly the structure of toxic AGEs (TAGE), show significant toxicity on cortical neuronal cells and that the neurotoxic effect of diabetic serum is completely blocked by neutralizing antibody against the AGE-2 epitope. Moreover, in human AD brains, AGE-2 is distributed in the cytosol of neurons in the hippocampus and parahippocampal gyrus. These results suggest that TAGE is involved in the pathogenesis of AD as well as other age-related diseases. In this review, the authors discuss the molecular mechanisms of AD, especially focusing on TAGE-RAGE system.
KW - Advanced glycation end product (AGEs)
KW - Alzheimer's disease (AD)
KW - Diabetic complications
KW - Glyceraldehyde-derived AGEs (AGE-2)
KW - Receptor for AGEs (RAGE)
KW - Toxic AGE (TAGE)
UR - http://www.scopus.com/inward/record.url?scp=33745877172&partnerID=8YFLogxK
U2 - 10.1177/1533317506289277
DO - 10.1177/1533317506289277
M3 - Review article
C2 - 16869341
AN - SCOPUS:33745877172
SN - 1533-3175
VL - 21
SP - 197
EP - 208
JO - American Journal of Alzheimer's Disease and other Dementias
JF - American Journal of Alzheimer's Disease and other Dementias
IS - 3
ER -