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Cell Mol Neurobiol ; 40(7): 1231-1242, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32140899

RESUMO

Recent studies demonstrated that FoxO3 circular RNA (circFoxO3) plays an important regulatory role in tumourigenesis and cardiomyopathy. However, the role of circFoxO3 in neurodegenerative diseases remains unknown. The aim of this study was to examine the possible role of circFoxO3 in neurodegenerative diseases and the underlying mechanisms. To model human neurodegenerative conditions, hippocampus-derived neurons were treated with glutamate. Using molecular and cellular biology approaches, we found that circFoxO3 expression was significantly higher in the glutamate treatment group than that in the control group. Furthermore, silencing of circFoxO3 protected HT22 cells from glutamate-induced oxidative injury through the inhibition of the mitochondrial apoptotic pathway. Collectively, our study demonstrates that endogenous circFoxO3 plays a key role in inducing apoptosis and neuronal cell death and may act as a novel therapeutic target for neurodegenerative diseases.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Hipocampo/metabolismo , Mitocôndrias/metabolismo , RNA Circular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteína Forkhead Box O3/genética , Ácido Glutâmico/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
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