| Literature DB >> 18391946 |
Diego E Berman1, Claudia Dall'Armi, Sergey V Voronov, Laura Beth J McIntire, Hong Zhang, Ann Z Moore, Agniezka Staniszewski, Ottavio Arancio, Tae-Wan Kim, Gilbert Di Paolo.
Abstract
Synaptic dysfunction caused by oligomeric assemblies of amyloid-beta peptide (Abeta) has been linked to cognitive deficits in Alzheimer's disease. Here we found that incubation of primary cortical neurons with oligomeric Abeta decreases the level of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2), a phospholipid that regulates key aspects of neuronal function. The destabilizing effect of Abeta on PtdIns(4,5)P2 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)P2 phosphatase in the brain and at the synapses. We also found that the inhibitory effect of Abeta on hippocampal long-term potentiation was strongly suppressed in slices from Synj1+/- mice, suggesting that Abeta-induced synaptic dysfunction can be ameliorated by treatments that maintain the normal PtdIns(4,5)P2 balance in the brain.Entities:
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Year: 2008 PMID： 18391946 PMCID： PMC2532986 DOI： 10.1038/nn.2100
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884