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HERO ID
6794279
Reference Type
Journal Article
Title
Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice
Author(s)
Dineley, KT; Hogan, D; Zhang, WenRu; Taglialatela, G; ,
Year
2007
Is Peer Reviewed?
1
Journal
Neurobiology of Learning and Memory
ISSN:
1074-7427
EISSN:
1095-9564
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Location
SAN DIEGO
Page Numbers
217-224
PMID
17521929
DOI
10.1016/j.nlm.2007.03.010
Web of Science Id
WOS:000249347700008
Abstract
Misfolded amyloid beta peptide (A beta) is a pathological hallmark of Alzheimer's disease (AD), a neurodegenerative illness characterized by cognitive deficits and neuronal loss. Transgenic mouse models of A beta over-production indicate that A beta-induced cognitive deficits occur in the absence of overt neuronal death, suggesting that while extensive neuronal death may be associated with later stages of the human disease, subtle physiological changes may underlie initial cognitive deficits. Therefore, identifying signaling elements involved in those A beta-induced cognitive impairments that occur prior to loss of neurons may reveal new potential pharmacological targets. Here, we report that the enzymatic activity of calcineurin, a key protein phosphatase involved in phosphorylation-dependent kinase activity crucial for synaptic plasticity and memory function, is upregulated in the CNS of the Tg2576 animal model for A beta over-production. Furthermore, acute treatment of Tg2576 mice with the calcineurin inhibitor FK506 (10 mg/kg i.p.) improves memory function. These results indicate that calcineurin may mediate some of the cognitive effects of excess A beta such that inhibition of calcineurin shall be further explored as a potential treatment to reverse cognitive impairments in AD. (C) 2007 Elsevier Inc. All rights reserved.
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