Unraveling the molecular mechanisms of Ace2-mediated post-COVID-19 cognitive dysfunction through systems genetics approach.
Exp Neurol
; 381: 114921, 2024 Nov.
Article
en En
| MEDLINE
| ID: mdl-39142369
ABSTRACT
The dysregulation of Angiotensin-converting enzyme 2 (ACE2) in central nervous system is believed associates with COVID-19 induced cognitive dysfunction. However, the detailed mechanism remains largely unknown. In this study, we performed a comprehensive system genetics analysis on hippocampal ACE2 based on BXD mice panel. Expression quantitative trait loci (eQTLs) mapping showed that Ace2 was strongly trans-regulated, and the elevation of Ace2 expression level was significantly correlated with impaired cognitive functions. Further Gene co-expression analysis showed that Ace2 may be correlated with the membrane proteins in Calcium signaling pathway. Further, qRT-PCR confirmed that SARS-CoV-2 spike S1 protein upregulated ACE2 expression together with eight membrane proteins in Calcium Signaling pathway. Moreover, such elevation can be attenuated by recombinant ACE2. Collectively, our findings revealed a potential mechanism of Ace2 in cognitive dysfunction, which could be beneficial for COVID-19-induced cognitive dysfunction prevention and potential treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sitios de Carácter Cuantitativo
/
Disfunción Cognitiva
/
Enzima Convertidora de Angiotensina 2
/
COVID-19
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Exp Neurol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos