Role of Acetylcholinesterase Inhibitors in the Metabolism of Amyloid Precursor Protein

被引:44
作者
Pakaski, M. [1 ]
Kasa, P. [1 ]
机构
[1] Univ Szeged, Fac Med, Albert Szent Gyorgyi Ctr Med & Pharmaceut Sci, Dept Psychiat,Alzheimers Dis Res Ctr, Szeged, Hungary
关键词
Alzheimer's disease; acetylcholinesterase inhibitor; amyloid precursor protein; protein kinase C; cholinergic receptors; alpha-secretase; signal transduction;
D O I
10.2174/1568007033482869
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Potentiation of central cholinergic activity has been proposed as a therapeutic approach for improving the cognitive function in patients with Alzheimer's disease (AD). Increasing the acetylcholine concentration in the brain by modulating acetylcholine-sterase (AChE) activity is among the most promising therapeutic strategies. Efforts to treat the underlying pathology based on the modulation of amyloid precursor protein (APP) processing in order to decrease the accumulation of beta-amyloid are also very important. Alterations in APP metabolism have recently been proposed to play a key role in the long-lasting effects of AChE inhibitors. This review surveys recent data from in vivo and in vitro studies that have contributed to our understanding of the role of AChE inhibitors in APP processing. The regulatory mechanisms relating to the muscarinic agonist effect, protein kinase C activation and mitogen-activated protein kinase phosphorylation, involving the alpha-secretase or the 5'-UTR region of the APP gene, are also discussed. Further work is warranted to elucidate the exact roles in APP metabolism of the AChE inhibitors used in AD therapy at present.
引用
收藏
页码:163 / 171
页数:9
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