Overexpression of MTERF4 promotes the amyloidogenic processing of APP by inhibiting ADAM10.
Biochem Biophys Res Commun
; 482(4): 928-934, 2017 Jan 22.
Article
em En
| MEDLINE
| ID: mdl-27894840
ABSTRACT
Alzheimer's disease (AD) is characterized by the deposition of ß-amyloid (Aß) peptide in the brain, which is produced by the proteolysis of ß-amyloid precursor protein (APP). Recently, the mitochondrial transcription factor 4 (MTERF4), a member of the MTERF family, was implicated in regulating mitochondrial DNA transcription and directly in controlling mitochondrial ribosomal translation. The present study identified a novel role for MTERF4 in shifting APP processing toward the amyloidogenic pathway. The levels of MTERF4 protein were significantly increased in the hippocampus of APP/PS1 mice. In addition, the overexpression of MTERF4 induced a significant increase in the levels of APP protein and secreted Aß42 in HEK293-APPswe cells compared with control cells. Further, MTERF4 overexpression shifted APP processing from α-to ß-cleavage, as indicated by decreased C83 levels and elevated C99 levels. Finally, the MTERF4 overexpression suppressed a disintegrin and metalloproteinase 10 (ADAM10) expression via a transcriptional mechanism. Taken together, these results suggest that MTERF4 promotes the amyloidogenic processing of APP by inhibiting ADAM10 in HEK293-APPswe cells; therefore, MTERF4 may play an important role in the pathogenesis of AD.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Regulação para Cima
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Precursor de Proteína beta-Amiloide
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Proteínas Mitocondriais
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Doença de Alzheimer
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Proteína ADAM10
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article