Mutant presenilin 2 increases acetylcholinesterase activity in neuronal cells.
A presenilin 2 mutation is believed to be involved in the development of Alzheimer's disease. In addition, transgenic mice with a presenilin 2 mutation have been reported to have learning and memory impairments. In this study, exposing PC12 cells expressing mutant presenilin 2 to 50 microM AP25-35, 30 mM L-glutamate and 50 microM H2O2 caused a significant increase in acetylcholine esterase activity. An in vivo study revealed high levels of this enzyme activity in the mutant presenilin 2 transgenic brains compared with the wild type presenilin 2 transgenic and nontransgenic samples. These results suggest that a mutant presenilin 2-induced neurodegeneration in Alzheimer's disease might be involved in the increase in acetylcholinesterase activity. These findings might help in the development of an appropriate therapeutic intervention targeting mutant presenilin 2-induced Alzheimer's disease.
Nguyen
Hong Nga
HN
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Hwang
Dae Youn
DY
Kim
Young Kyu
YK
Yoon
Do Young
DY
Kim
Jae Hwa
JH
Lee
Moon Soon
MS
Lee
Myung Koo
MK
Yun
Yeo Pyo
YP
Oh
Ki Wan
KW
Hong
Jin Tae
JT
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology; D000818:Animals; D001921:Brain / Q000201:enzymology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000201:enzymology*; D016716:PC12 Cells; D053766:Presenilin-2; D051381:Rats
D008565:Membrane Proteins; D053766:Presenilin-2; D000110:Acetylcholinesterase