LTP and memory impairment caused by extracellular Aß and Tau oligomers is APP-dependent.
Elife
; 62017 07 11.
Article
em En
| MEDLINE
| ID: mdl-28696204
ABSTRACT
The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oAß) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oAß and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oAß, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oAß and oTau requires expression of APP. Finally, the toxic effect of both extracellular oAß and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oAß- and oTau-induced defects in spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic target against Alzheimer's Disease (AD) and a host of other neurodegenerative diseases characterized by abnormal levels of Aß and/or Tau.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Precursor de Proteína beta-Amiloide
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Proteínas tau
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Potenciação de Longa Duração
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Multimerização Proteica
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Transtornos da Memória
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Neurônios
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article