The role of the phosphoinositide signalling system in the pathogenesis of sporadic Alzheimer's disease: a hypothesis

被引:20
作者
Fowler, CJ [1 ]
机构
[1] Umea Univ, Dept Pharmacol, S-90187 Umea, Sweden
关键词
Alzheimer's disease; signal transduction; inositol (1,4,5) trisphosphate; protein kinase C; oxidative stress; beta-amyloid;
D O I
10.1016/S0165-0173(97)00024-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Great advances have been made in recent years in our knowledge of the genetic mutations found in early onset familial Alzheimer's disease (AD) and their pathological consequences. The pathogenesis of sporadic AD, on the other hand, is less clear, although a central role of oxidative stress is indicated. In the AD brain, severe dysfunctions in the phosphoinositide signalling pathway have been reported. In view of the fact that (a) oxidative stress can adversely affect phosphoinositide breakdown and hence diacylglycerol-mediated activation of protein kinase C and (b) protein kinase C activation reduces the production of P-amyloid peptide from amyloid precursor protein, it is possible that this represents a pathogenic pathway whereby oxidative stress can lead to amyloid deposition and the development of the disease. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:373 / 380
页数:8
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