Regulation of Neurotransmitter Release by Amyloid Precursor Protein Through Synapsin Phosphorylation.
Neurochem Res
; 44(3): 683-691, 2019 Mar.
Article
em En
| MEDLINE
| ID: mdl-29052089
ABSTRACT
Abnormal processing of amyloid precursor protein (APP) and aggregation of the Aß peptide are known to play a key role in the pathogenesis of Alzheimer disease, but the function of endogenous APP under normal physiological conditions remains poorly understood. In this study, we investigated presynaptic changes in APP knockout (KO) mice. We demonstrate that both sucrose-induced neurotransmission and synaptic depletion in response to high frequency stimulation are significantly enhanced in APP KO compared to wild type littermates. In addition, the level of phosphorylated forms of synapsins, but not total synapsins, is elevated in the KO mice. Furthermore, we show that the inhibition of L-type calcium channels normalizes phosphorylated synapsins and slows down the high frequency induced synaptic depletion in APP KO mice. These results suggest a new mechanism by which APP regulates synaptic vesicle dynamics through synapsin-dependent phosphorylation.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fosforilação
/
Vesículas Sinápticas
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Sinapsinas
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Precursor de Proteína beta-Amiloide
Limite:
Animals
Idioma:
En
Revista:
Neurochem Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China