p75NTR enhances cognitive dysfunction in a mouse Alzheimer's disease model by inhibiting microRNA-210-3p-mediated PCYT2 through activation of NF-κB.
Int J Biol Macromol
; 225: 404-415, 2023 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-36379282
ABSTRACT
Alzheimer's disease (AD) is a main cause of dementia and exhibits abnormality in cognitive behaviors. Here, we probed into the role of p75 neurotrophin receptor (p75NTR) in cognitive dysfunction in AD. Primarily, C57BL/6 mouse and neuroblastoma cells were treated by amyloid-beta1-42 (Aß1-42), respectively, to establish the in vivo and in vitro models of AD. The downstream genes of p75NTR were predicted by RNA-sequencing and bioinformatics analysis. Then the interaction among p75NTR, nuclear factor kappa B (NF-κB), microRNA-210-3p (miR-210-3p) and phosphoethanolamine cytidylyltransferase 2 (PYCT2) was verified, followed by analysis of their effects on cognitive behaviors and biological characteristics of hippocampal neurons of mouse with AD-like symptoms. p75NTR knockout alleviated cognitive dysfunction in mice with AD-like symptoms and reduced Aß1-42-induced hippocampal neuron damage and apoptosis. p75NTR up-regulated miR-210-3p expression by activating NF-κB, thereby limiting PCYT2 expression. PCYT2 silencing in p75NTR-/- mice promoted neuronal apoptosis and aggravated cognitive dysfunction in AD mouse models. In summary, p75NTR is capable of accelerating cognitive dysfunction in AD by mediating the NF-κB/miR-210-3p/PCYT2 axis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Enfermedad de Alzheimer
/
Disfunción Cognitiva
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Biol Macromol
Año:
2023
Tipo del documento:
Article
País de afiliación:
China