Neuroprotection induced by Navß2knockdown in APP/PS1 transgenic neurons is associated with NEP regulation.
Mol Med Rep
; 20(2): 2002-2011, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-31257483
ABSTRACT
Voltagegated sodium channel ß2 (Navß2), as an unconventional substrate of ßsite amyloid precursor protein cleaving enzyme 1, is involved in regulating the neuronal surface expression of sodium channels. A previous study demonstrated that knockdown of Navß2 protected neurons and induced spatial cognition improvement by partially reducing pathological amyloidogenic processing of amyloid precursor protein (APP) in aged APP/presenilin 1 (PS1) transgenic mice. The present study aimed to investigate whether Navß2 knockdown altered APP metabolism via regulation of the Aßdegrading enzyme neprilysin (NEP). APPswe/PS1ΔE9 mice (APP/PS1 transgenic mice with a C57BL/6J genetic background) carrying a Navß2knockdown mutation (APP/PS1/Navß2kd) or without Navß2 knockdown (APP/PS1) were used for cell culture and further analysis. The present results demonstrated that in APP/PS1 mousederived neurons, Navß2 knockdown partially reversed the reduction in pathological APP cleavage, and the recovery of neurite extension and neuron area. Additionally, Navß2 knockdown increased NEP activity and levels, and the levels of intracellular domain fragment binding to the NEP promoter. The present findings suggested that knockdown of Navß2 reversed the APP/PS1 mutationinduced deficiency in amyloid ß degradation by regulating NEP.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Presenilina-1
/
Subunidade beta-2 do Canal de Sódio Disparado por Voltagem
/
Neuroproteção
/
Neurônios
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article