Oligomeric amyloid-β peptide disrupts phosphatidylinositol-4,5-bisphosphate metabolism

被引：156

作者：

Berman, Diego E. ^{[1
]}

Dall'Armi, Claudia ^{[1
]}

Voronov, Sergey V. ^{[1
]}

McIntire, Laura Beth J. ^{[1
]}

Zhang, Hong ^{[1
]}

Moore, Ann Z. ^{[1
]}

Staniszewski, Agniezka ^{[1
]}

Arancio, Ottavio ^{[1
]}

Kim, Tae-Wan ^{[1
]}

Di Paolo, Gilbert ^{[1
]}

机构：

[1] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, Coll Phys & Surg,Dept Pathol & Cell Biol, New York, NY 10032 USA

来源：

NATURE NEUROSCIENCE | 2008年 / 11卷 / 05期

关键词：

D O I：

10.1038/nn.2100

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Synaptic dysfunction caused by oligomeric assemblies of amyloid-beta peptide (A beta) has been linked to cognitive deficits in Alzheimer's disease. Here we found that incubation of primary cortical neurons with oligomeric A beta decreases the level of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P-2), a phospholipid that regulates key aspects of neuronal function. The destabilizing effect of A beta on PtdIns(4,5)P-2 metabolism was Ca2+-dependent and was not observed in neurons that were derived from mice that are haploinsufficient for Synj1. This gene encodes synaptojanin 1, the main PtdIns(4,5)P-2 phosphatase in the brain and at the synapses. We also found that the inhibitory effect of A beta on hippocampal long-term potentiation was strongly suppressed in slices from Synj1(+/-) mice, suggesting that A beta-induced synaptic dysfunction can be ameliorated by treatments that maintain the normal PtdIns(4,5)P-2 balance in the brain.

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页码：547 / 554

页数：8

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