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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-49409

Knobloch, M; Farinelli, M; Konietzko, U; Nitsch, R M; Mansuy, I M (2007). Abeta oligomer-mediated long-term potentiation impairment involves protein phosphatase 1-dependent mechanisms. Journal of Neuroscience, 27(29):7648-7653.

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Abstract

Amyloid beta (Abeta) oligomers are derived from proteolytic cleavage of amyloid precursor protein (APP) and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. The mechanisms underlying such toxicity on synaptic functions are complex and not fully understood. Here, we provide the first evidence that these mechanisms involve protein phosphatase 1 (PP1). Using a novel transgenic mouse model expressing human APP with the Swedish and Arctic mutations that render Abeta more prone to form oligomers (arcAbeta mice), we show that the LTP impairment induced by Abeta oligomers can be fully reversed by PP1 inhibition in vitro. We further demonstrate that the genetic inhibition of endogenous PP1 in vivo confers resistance to Abeta oligomer-mediated toxicity and preserves LTP. Overall, these results reveal that PP1 is a key player in the mechanisms of AD pathology.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
DDC:610 Medicine & health
Language:English
Date:2007
Deposited On:06 Sep 2011 08:33
Last Modified:16 Jul 2014 20:11
Publisher:Society for Neuroscience
ISSN:0270-6474
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1523/JNEUROSCI.0395-07.2007
PubMed ID:17634359
Citations:Web of Science®. Times Cited: 64
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Scopus®. Citation Count: 66

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